The AAGGG repeat expansion in RFC1 associated with late-onset ataxia and sensory neuropathy: from genetic cause to defining the functional mechanism
Lead Research Organisation:
University College London
Department Name: Institute of Neurology
Abstract
Late-onset ataxia is a common reason for neurological consultation, but its cause often remains idiopathic. Ataxia primarily results from cerebellar dysfunction but can also be caused by disorders affecting the large-fibre sensory neurons (sensory neuronopathy) or the vestibular system. When in combination, this more severe late onset ataxia is termed cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). We identified a biallelic intronic AAGGG repeat expansion in the replication factor C subunit 1 (RFC1) as a common cause of CANVAS and late-onset ataxia. The AAGGG repeat expansion does not lead to overt loss of function of RFC1, which is unexpected given the recessive pattern of inheritance of the disease and suggests that novel disease-causing mechanisms could be involved. The main objective of this project is to
investigate the molecular mechanisms underlying neurodegeneration in the presence of biallelic AAGGG expansions in RFC1. We will use a combined approach by taking advantage of in vitro experiments, Drosophila model as well as patients'-derived cell lines and tissues in order to test the presence of a dose-dependent gain-of-function of toxic pentapeptide repeat proteins encoded by the transcribed intronic repeated sequence and/or unconventional loss-of-function of tissue specific RFC1 isoforms, non-coding transcripts, neighboring and distant genes and/or reorganization 3D chromatin structure.
investigate the molecular mechanisms underlying neurodegeneration in the presence of biallelic AAGGG expansions in RFC1. We will use a combined approach by taking advantage of in vitro experiments, Drosophila model as well as patients'-derived cell lines and tissues in order to test the presence of a dose-dependent gain-of-function of toxic pentapeptide repeat proteins encoded by the transcribed intronic repeated sequence and/or unconventional loss-of-function of tissue specific RFC1 isoforms, non-coding transcripts, neighboring and distant genes and/or reorganization 3D chromatin structure.
Technical Summary
Late-onset ataxia is a common reason for neurological consultation, but its cause often remains idiopathic. Ataxia primarily results from cerebellar dysfunction but can also be caused by disorders affecting the large-fibre sensory neurons (sensory neuronopathy) or the vestibular system. When in combination, this more severe late onset ataxia is termed cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). We identified a biallelic intronic AAGGG repeat expansion in the replication factor C subunit 1 (RFC1) as a common cause of CANVAS and late-onset ataxia. The AAGGG repeat expansion does not lead to overt loss of function of RFC1, which is unexpected given the recessive pattern of inheritance of the disease and suggests that novel disease-causing mechanisms could be involved. Main objective of this project is to
investigate the molecular mechanisms underlying neurodegeneration in the presence of biallelic AAGGG expansions in RFC1. We will use a combinational approach by taking advantage in vitro and Drosophila models as well as patients'-derived cell lines and tissues in order to test the presence of a dose-dependent gain-of-function of toxic pentapeptide repeat proteins encoded by the transcribed intronic repeated sequence and/or unconventional loss-of-function of tissue specific RFC1 isoforms, non-coding transcripts, neighbouring and distant genes and/or reorganization of topologically associated domains and 3D chromatin structure.
investigate the molecular mechanisms underlying neurodegeneration in the presence of biallelic AAGGG expansions in RFC1. We will use a combinational approach by taking advantage in vitro and Drosophila models as well as patients'-derived cell lines and tissues in order to test the presence of a dose-dependent gain-of-function of toxic pentapeptide repeat proteins encoded by the transcribed intronic repeated sequence and/or unconventional loss-of-function of tissue specific RFC1 isoforms, non-coding transcripts, neighbouring and distant genes and/or reorganization of topologically associated domains and 3D chromatin structure.
Planned Impact
The frequency of the repeat expansion in 20% of undiagnosed ataxia cases and almost over 90% of typical CANVAS cases together with a carrier rate in the healthy population of ~1% makes the AAGGG repeat expansion in RFC1 as the most common cause of late-onset recessive ataxia. Therefore, we predict that the results of the study will be of great interest to the neurogenetics community and to the field of repeat expansion disorders, both at clinical and laboratory level.
Repeat expansions are still relatively hard to find and they may account for a relatively large proportion of missing heritability in neurological and non-neurological disorders. The majority of repeat expansions were discovered by positional cloning approaches and next generation sequencing technologies have so far had a limited impact on their identification. Our approach has unravelled that a significant part of undiagnosed ataxia and sensory neuronopathy cases is caused by a recessive repeat expansion, and we think that, if combined with novel tools for analysis of STR from WGS data (eg Expansion Hunter), it could inspire other researchers in academia or other research institutions, such as Genomic England, in the discovery of other recessive repeat expansion disorders.
Understandably, given the early days of this novel repeat expansion, little is known about the associated disease-causing mechanisms of this as well as other penta- and exanucleotide repeat disorders. However, this area has gained great importance as shown by the exponential growth of work following the discovery of GGGGCC expansion in c9orf72 in ALS/FTD and we now stand in the unique position to be the first ones to address the same mechanistic questions in this common type of recessive ataxia.
If confirmed, our hypothesis of a dose (and age) dependent toxic gain-of-function of AAGGG repeat expansion in RFC1 will represent a completely novel pathogenic mechanisms underlying a late-onset recessive Mendelian disorder, with broader implications to the general field of neurodegenerative diseases.
Moreover, the modified protocol we designed for recursive directional ligation, given the independence of restriction digestion and subsequent ligation from the repeated unit sequence, has the potential to enable the generation of increased repeat sizes of any nucleotide sequence and could represent a useful tool to basic scientists working on repeat expansion disorders and non-coding repetitive DNA elements.
Finally, one of the main aims of the project is to establish in vitro, cellular and Drosophila models of the disease which will be of use not only to the academic community but also to the pharmaceutical industry in order to test possible ways of future therapeutic intervention.
Repeat expansions are still relatively hard to find and they may account for a relatively large proportion of missing heritability in neurological and non-neurological disorders. The majority of repeat expansions were discovered by positional cloning approaches and next generation sequencing technologies have so far had a limited impact on their identification. Our approach has unravelled that a significant part of undiagnosed ataxia and sensory neuronopathy cases is caused by a recessive repeat expansion, and we think that, if combined with novel tools for analysis of STR from WGS data (eg Expansion Hunter), it could inspire other researchers in academia or other research institutions, such as Genomic England, in the discovery of other recessive repeat expansion disorders.
Understandably, given the early days of this novel repeat expansion, little is known about the associated disease-causing mechanisms of this as well as other penta- and exanucleotide repeat disorders. However, this area has gained great importance as shown by the exponential growth of work following the discovery of GGGGCC expansion in c9orf72 in ALS/FTD and we now stand in the unique position to be the first ones to address the same mechanistic questions in this common type of recessive ataxia.
If confirmed, our hypothesis of a dose (and age) dependent toxic gain-of-function of AAGGG repeat expansion in RFC1 will represent a completely novel pathogenic mechanisms underlying a late-onset recessive Mendelian disorder, with broader implications to the general field of neurodegenerative diseases.
Moreover, the modified protocol we designed for recursive directional ligation, given the independence of restriction digestion and subsequent ligation from the repeated unit sequence, has the potential to enable the generation of increased repeat sizes of any nucleotide sequence and could represent a useful tool to basic scientists working on repeat expansion disorders and non-coding repetitive DNA elements.
Finally, one of the main aims of the project is to establish in vitro, cellular and Drosophila models of the disease which will be of use not only to the academic community but also to the pharmaceutical industry in order to test possible ways of future therapeutic intervention.
Organisations
- University College London (Fellow, Lead Research Organisation)
- University of Milan (Collaboration)
- Universidade de São Paulo (Collaboration)
- University of Pavia (Collaboration)
- Pitié-Salpêtrière Hospital (Collaboration)
- University of Miami (Collaboration)
- University of Perth (Collaboration)
- Sheffield Teaching Hospitals NHS Foundation Trust (Collaboration)
- UNIVERSITY OF SYDNEY (Collaboration)
- University Hospital Tuebingen (Collaboration)
Publications
Hadjivassiliou M
(2024)
Can CANVAS due to RFC1 biallelic expansions present with pure ataxia?
in Journal of Neurology, Neurosurgery & Psychiatry
Huin V
(2022)
Motor neuron pathology in CANVAS due to RFC1 expansions.
in Brain : a journal of neurology
Kumar KR
(2020)
RFC1 expansions can mimic hereditary sensory neuropathy with cough and Sjögren syndrome.
in Brain : a journal of neurology
Lam T
(2023)
Repeat expansions in NOP56 are a cause of spinocerebellar ataxia Type 36 in the British population.
in Brain communications
Martín-Aguilar L
(2022)
Clinical and Laboratory Features in Anti-NF155 Autoimmune Nodopathy.
in Neurology(R) neuroimmunology & neuroinflammation
Meindl T
(2020)
[CANVAS: case report on a novel repeat expansion disorder with late-onset ataxia].
in Der Nervenarzt
Novis LE
(2024)
Unraveling the genetic landscape of undiagnosed cerebellar ataxia in Brazilian patients.
in Parkinsonism & related disorders
O'Donnell LF
(2022)
Exploratory analysis of lower limb muscle MRI in a case series of patients with SORD neuropathy.
in Journal of neurology, neurosurgery, and psychiatry
Pagnamenta AT
(2021)
An ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy.
in Brain : a journal of neurology
Pellerin D
(2024)
Intronic FGF14 GAA repeat expansions are a common cause of ataxia syndromes with neuropathy and bilateral vestibulopathy.
in Journal of neurology, neurosurgery, and psychiatry
Description | A randomised, double-blind, placebo-controlled, two-part study to evaluate the pharmacodynamic efficacy and clinical benefit of AT- 007 in patients with Sorbitol Dehydrogenase (SORD) Deficiency (Protocol #: AT-007-1005) |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Contribution to new or improved professional practice |
URL | https://appliedtherapeutics.gcs-web.com/news-releases/news-release-details/applied-therapeutics-anno... |
Description | National Genomic Test Directory application to include RFC1 as a NHS diagnostic test |
Geographic Reach | National |
Policy Influence Type | Contribution to a national consultation/review |
Impact | RFC1 will be included as part of the other neuropathy and ataxia panels, R54 and R78. Also a bespoke PCR based test in selected cases is being considered given the high prevalence of the disease |
Description | Clinical Research Collaboration Agreement with Applied Therapeutics |
Amount | $289,000 (USD) |
Organisation | University College London |
Sector | Academic/University |
Country | United Kingdom |
Start | 09/2022 |
End | 03/2025 |
Description | NIH Inherited Neuropathy Consortium Pilot Award. Project title: Untangling the genomics of axonal Charcot- Marie-Tooth disease |
Amount | $50,000 (USD) |
Organisation | National Institutes of Health (NIH) |
Sector | Public |
Country | United States |
Start | 01/2021 |
End | 12/2022 |
Description | Research Seed Money |
Amount | $840,000 (USD) |
Organisation | University College London |
Sector | Academic/University |
Country | United Kingdom |
Start | 03/2024 |
End | 03/2027 |
Description | Genotype and phenotype spectrum of RFC1 CANVAS and disease spectrum |
Organisation | Pitié-Salpêtrière Hospital |
Country | France |
Sector | Hospitals |
PI Contribution | As stated in the project proposal, we partnered with several centres around the world to fully define the genotype and phenotype spectrum RFC1 disease. We have tested over the last year over 2000 samples with ataxia and/or sensory neuropathy for RFC1 expansion sent to us from all across the world, as shown in the research output. Identification of novel population specific pathogenic configuration in RFC1 |
Collaborator Contribution | Contribution with patients samples and clinical information. |
Impact | University of Perth Beecroft S. J., Cortese A., Sullivan R., Yau W. Y., Dyer Z., Wu T. Y., Mulroy E., Pelosi L., Rodrigues M., Taylor R., Mossman S., Leadbetter R., Cleland J.,Anderson T., Ravenscroft G., Laing N. G., Houlden H., Reilly M. M., Roxburgh R. H. (2020). A Maori specific RFC1 pathogenic repeat configuration in CANVAS, likely due to a founder allele. BRAIN (ONLINE), vol. 143, p. 2673-2680, ISSN: 1460-2156, doi: 10.1093/brain/awaa203 Scriba C. K., Beecroft S. J., Clayton J. S., Cortese A., Sullivan R., Yau W. Y., Dominik N., Rodrigues M., Walker E., Dyer Z., Wu T. Y., Davis M. R., Chandler D. C., Weisburd B., Houlden H., Reilly M. M., Laing N. G., Lamont P. J., Roxburgh R. H., Ravenscroft G. (2020). A novel RFC1 repeat motif (ACAGG) in two Asia-Pacific CANVAS families. BRAIN (ONLINE), vol. 143, p. 2904- 2910, ISSN: 1460-2156, doi: 10.1093/brain/awaa263 University of Sydney Kumar K. R*., Cortese A*., Tomlinson S. E., Efthymiou S., Ellis M., Zhu D., Stoll M., Dominik N., Tisch S., Tchan M., Wu K. H. C., Devery S., Spring P. J., Hawke S., Cremer P., Ng K., Reilly M. M., Nicholson G. A., Houlden H., Kennerson M. (2020). RFC1 expansions can mimic hereditary sensory neuropathy with cough and Sjögren syndrome. BRAIN (ONLINE), vol. 143, p. e82, ISSN: 1460-2156, doi: 10.1093/brain/awaa244 University of Tubingen and collaborators of ARCA consortium Traschütz A, Cortese A, Reich S, Dominik N, Faber J, Jacobi H, Hartmann AM, Rujescu D, Montaut S, Echaniz-Laguna A, Erer S, Schütz VC, Tarnutzer AA, Sturm M, Haack TB, Vaucamps-Diedhiou N, Puccio H, Schöls L, Klockgether T, van de Warrenburg BP, Paucar M, Timmann D, Hilgers RD, Gazulla J, Strupp M, Moris G, Filla A, Houlden H, Anheim M, Infante J, Basak AN, Synofzik M; RFC1 Study Group.Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1 Disease. Neurology. 2021 Mar 2;96(9):e1369-e1382. doi: 10.1212/WNL.0000000000011528. Epub 2021 Jan 25. Paris - Pitie'-Salpetriere Cortese A., Tozza S., Yau W. Y., Rossi S., Beecroft S. J., Jaunmuktane Z., Dyer Z., Ravenscroft G., Lamont P. J., Mossman S., Chancellor A., Maisonobe T., Pereon Y., Cauquil C., Colnaghi S., Mallucci [...] H., Houlden H., Reilly M. M. (2020). Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion. BRAIN, vol. 143, p. 489-490, ISSN: 0006-8950, doi: 10.1093/brain/awz418 |
Start Year | 2020 |
Description | Genotype and phenotype spectrum of RFC1 CANVAS and disease spectrum |
Organisation | Sheffield Teaching Hospitals NHS Foundation Trust |
Department | Sheffield Podiatry Services |
Country | United Kingdom |
Sector | Public |
PI Contribution | As stated in the project proposal, we partnered with several centres around the world to fully define the genotype and phenotype spectrum RFC1 disease. We have tested over the last year over 2000 samples with ataxia and/or sensory neuropathy for RFC1 expansion sent to us from all across the world, as shown in the research output. Identification of novel population specific pathogenic configuration in RFC1 |
Collaborator Contribution | Contribution with patients samples and clinical information. |
Impact | University of Perth Beecroft S. J., Cortese A., Sullivan R., Yau W. Y., Dyer Z., Wu T. Y., Mulroy E., Pelosi L., Rodrigues M., Taylor R., Mossman S., Leadbetter R., Cleland J.,Anderson T., Ravenscroft G., Laing N. G., Houlden H., Reilly M. M., Roxburgh R. H. (2020). A Maori specific RFC1 pathogenic repeat configuration in CANVAS, likely due to a founder allele. BRAIN (ONLINE), vol. 143, p. 2673-2680, ISSN: 1460-2156, doi: 10.1093/brain/awaa203 Scriba C. K., Beecroft S. J., Clayton J. S., Cortese A., Sullivan R., Yau W. Y., Dominik N., Rodrigues M., Walker E., Dyer Z., Wu T. Y., Davis M. R., Chandler D. C., Weisburd B., Houlden H., Reilly M. M., Laing N. G., Lamont P. J., Roxburgh R. H., Ravenscroft G. (2020). A novel RFC1 repeat motif (ACAGG) in two Asia-Pacific CANVAS families. BRAIN (ONLINE), vol. 143, p. 2904- 2910, ISSN: 1460-2156, doi: 10.1093/brain/awaa263 University of Sydney Kumar K. R*., Cortese A*., Tomlinson S. E., Efthymiou S., Ellis M., Zhu D., Stoll M., Dominik N., Tisch S., Tchan M., Wu K. H. C., Devery S., Spring P. J., Hawke S., Cremer P., Ng K., Reilly M. M., Nicholson G. A., Houlden H., Kennerson M. (2020). RFC1 expansions can mimic hereditary sensory neuropathy with cough and Sjögren syndrome. BRAIN (ONLINE), vol. 143, p. e82, ISSN: 1460-2156, doi: 10.1093/brain/awaa244 University of Tubingen and collaborators of ARCA consortium Traschütz A, Cortese A, Reich S, Dominik N, Faber J, Jacobi H, Hartmann AM, Rujescu D, Montaut S, Echaniz-Laguna A, Erer S, Schütz VC, Tarnutzer AA, Sturm M, Haack TB, Vaucamps-Diedhiou N, Puccio H, Schöls L, Klockgether T, van de Warrenburg BP, Paucar M, Timmann D, Hilgers RD, Gazulla J, Strupp M, Moris G, Filla A, Houlden H, Anheim M, Infante J, Basak AN, Synofzik M; RFC1 Study Group.Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1 Disease. Neurology. 2021 Mar 2;96(9):e1369-e1382. doi: 10.1212/WNL.0000000000011528. Epub 2021 Jan 25. Paris - Pitie'-Salpetriere Cortese A., Tozza S., Yau W. Y., Rossi S., Beecroft S. J., Jaunmuktane Z., Dyer Z., Ravenscroft G., Lamont P. J., Mossman S., Chancellor A., Maisonobe T., Pereon Y., Cauquil C., Colnaghi S., Mallucci [...] H., Houlden H., Reilly M. M. (2020). Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion. BRAIN, vol. 143, p. 489-490, ISSN: 0006-8950, doi: 10.1093/brain/awz418 |
Start Year | 2020 |
Description | Genotype and phenotype spectrum of RFC1 CANVAS and disease spectrum |
Organisation | Universidade de São Paulo |
Country | Brazil |
Sector | Academic/University |
PI Contribution | As stated in the project proposal, we partnered with several centres around the world to fully define the genotype and phenotype spectrum RFC1 disease. We have tested over the last year over 2000 samples with ataxia and/or sensory neuropathy for RFC1 expansion sent to us from all across the world, as shown in the research output. Identification of novel population specific pathogenic configuration in RFC1 |
Collaborator Contribution | Contribution with patients samples and clinical information. |
Impact | University of Perth Beecroft S. J., Cortese A., Sullivan R., Yau W. Y., Dyer Z., Wu T. Y., Mulroy E., Pelosi L., Rodrigues M., Taylor R., Mossman S., Leadbetter R., Cleland J.,Anderson T., Ravenscroft G., Laing N. G., Houlden H., Reilly M. M., Roxburgh R. H. (2020). A Maori specific RFC1 pathogenic repeat configuration in CANVAS, likely due to a founder allele. BRAIN (ONLINE), vol. 143, p. 2673-2680, ISSN: 1460-2156, doi: 10.1093/brain/awaa203 Scriba C. K., Beecroft S. J., Clayton J. S., Cortese A., Sullivan R., Yau W. Y., Dominik N., Rodrigues M., Walker E., Dyer Z., Wu T. Y., Davis M. R., Chandler D. C., Weisburd B., Houlden H., Reilly M. M., Laing N. G., Lamont P. J., Roxburgh R. H., Ravenscroft G. (2020). A novel RFC1 repeat motif (ACAGG) in two Asia-Pacific CANVAS families. BRAIN (ONLINE), vol. 143, p. 2904- 2910, ISSN: 1460-2156, doi: 10.1093/brain/awaa263 University of Sydney Kumar K. R*., Cortese A*., Tomlinson S. E., Efthymiou S., Ellis M., Zhu D., Stoll M., Dominik N., Tisch S., Tchan M., Wu K. H. C., Devery S., Spring P. J., Hawke S., Cremer P., Ng K., Reilly M. M., Nicholson G. A., Houlden H., Kennerson M. (2020). RFC1 expansions can mimic hereditary sensory neuropathy with cough and Sjögren syndrome. BRAIN (ONLINE), vol. 143, p. e82, ISSN: 1460-2156, doi: 10.1093/brain/awaa244 University of Tubingen and collaborators of ARCA consortium Traschütz A, Cortese A, Reich S, Dominik N, Faber J, Jacobi H, Hartmann AM, Rujescu D, Montaut S, Echaniz-Laguna A, Erer S, Schütz VC, Tarnutzer AA, Sturm M, Haack TB, Vaucamps-Diedhiou N, Puccio H, Schöls L, Klockgether T, van de Warrenburg BP, Paucar M, Timmann D, Hilgers RD, Gazulla J, Strupp M, Moris G, Filla A, Houlden H, Anheim M, Infante J, Basak AN, Synofzik M; RFC1 Study Group.Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1 Disease. Neurology. 2021 Mar 2;96(9):e1369-e1382. doi: 10.1212/WNL.0000000000011528. Epub 2021 Jan 25. Paris - Pitie'-Salpetriere Cortese A., Tozza S., Yau W. Y., Rossi S., Beecroft S. J., Jaunmuktane Z., Dyer Z., Ravenscroft G., Lamont P. J., Mossman S., Chancellor A., Maisonobe T., Pereon Y., Cauquil C., Colnaghi S., Mallucci [...] H., Houlden H., Reilly M. M. (2020). Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion. BRAIN, vol. 143, p. 489-490, ISSN: 0006-8950, doi: 10.1093/brain/awz418 |
Start Year | 2020 |
Description | Genotype and phenotype spectrum of RFC1 CANVAS and disease spectrum |
Organisation | University Hospital Tuebingen |
Country | Germany |
Sector | Academic/University |
PI Contribution | As stated in the project proposal, we partnered with several centres around the world to fully define the genotype and phenotype spectrum RFC1 disease. We have tested over the last year over 2000 samples with ataxia and/or sensory neuropathy for RFC1 expansion sent to us from all across the world, as shown in the research output. Identification of novel population specific pathogenic configuration in RFC1 |
Collaborator Contribution | Contribution with patients samples and clinical information. |
Impact | University of Perth Beecroft S. J., Cortese A., Sullivan R., Yau W. Y., Dyer Z., Wu T. Y., Mulroy E., Pelosi L., Rodrigues M., Taylor R., Mossman S., Leadbetter R., Cleland J.,Anderson T., Ravenscroft G., Laing N. G., Houlden H., Reilly M. M., Roxburgh R. H. (2020). A Maori specific RFC1 pathogenic repeat configuration in CANVAS, likely due to a founder allele. BRAIN (ONLINE), vol. 143, p. 2673-2680, ISSN: 1460-2156, doi: 10.1093/brain/awaa203 Scriba C. K., Beecroft S. J., Clayton J. S., Cortese A., Sullivan R., Yau W. Y., Dominik N., Rodrigues M., Walker E., Dyer Z., Wu T. Y., Davis M. R., Chandler D. C., Weisburd B., Houlden H., Reilly M. M., Laing N. G., Lamont P. J., Roxburgh R. H., Ravenscroft G. (2020). A novel RFC1 repeat motif (ACAGG) in two Asia-Pacific CANVAS families. BRAIN (ONLINE), vol. 143, p. 2904- 2910, ISSN: 1460-2156, doi: 10.1093/brain/awaa263 University of Sydney Kumar K. R*., Cortese A*., Tomlinson S. E., Efthymiou S., Ellis M., Zhu D., Stoll M., Dominik N., Tisch S., Tchan M., Wu K. H. C., Devery S., Spring P. J., Hawke S., Cremer P., Ng K., Reilly M. M., Nicholson G. A., Houlden H., Kennerson M. (2020). RFC1 expansions can mimic hereditary sensory neuropathy with cough and Sjögren syndrome. BRAIN (ONLINE), vol. 143, p. e82, ISSN: 1460-2156, doi: 10.1093/brain/awaa244 University of Tubingen and collaborators of ARCA consortium Traschütz A, Cortese A, Reich S, Dominik N, Faber J, Jacobi H, Hartmann AM, Rujescu D, Montaut S, Echaniz-Laguna A, Erer S, Schütz VC, Tarnutzer AA, Sturm M, Haack TB, Vaucamps-Diedhiou N, Puccio H, Schöls L, Klockgether T, van de Warrenburg BP, Paucar M, Timmann D, Hilgers RD, Gazulla J, Strupp M, Moris G, Filla A, Houlden H, Anheim M, Infante J, Basak AN, Synofzik M; RFC1 Study Group.Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1 Disease. Neurology. 2021 Mar 2;96(9):e1369-e1382. doi: 10.1212/WNL.0000000000011528. Epub 2021 Jan 25. Paris - Pitie'-Salpetriere Cortese A., Tozza S., Yau W. Y., Rossi S., Beecroft S. J., Jaunmuktane Z., Dyer Z., Ravenscroft G., Lamont P. J., Mossman S., Chancellor A., Maisonobe T., Pereon Y., Cauquil C., Colnaghi S., Mallucci [...] H., Houlden H., Reilly M. M. (2020). Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion. BRAIN, vol. 143, p. 489-490, ISSN: 0006-8950, doi: 10.1093/brain/awz418 |
Start Year | 2020 |
Description | Genotype and phenotype spectrum of RFC1 CANVAS and disease spectrum |
Organisation | University of Milan |
Country | Italy |
Sector | Academic/University |
PI Contribution | As stated in the project proposal, we partnered with several centres around the world to fully define the genotype and phenotype spectrum RFC1 disease. We have tested over the last year over 2000 samples with ataxia and/or sensory neuropathy for RFC1 expansion sent to us from all across the world, as shown in the research output. Identification of novel population specific pathogenic configuration in RFC1 |
Collaborator Contribution | Contribution with patients samples and clinical information. |
Impact | University of Perth Beecroft S. J., Cortese A., Sullivan R., Yau W. Y., Dyer Z., Wu T. Y., Mulroy E., Pelosi L., Rodrigues M., Taylor R., Mossman S., Leadbetter R., Cleland J.,Anderson T., Ravenscroft G., Laing N. G., Houlden H., Reilly M. M., Roxburgh R. H. (2020). A Maori specific RFC1 pathogenic repeat configuration in CANVAS, likely due to a founder allele. BRAIN (ONLINE), vol. 143, p. 2673-2680, ISSN: 1460-2156, doi: 10.1093/brain/awaa203 Scriba C. K., Beecroft S. J., Clayton J. S., Cortese A., Sullivan R., Yau W. Y., Dominik N., Rodrigues M., Walker E., Dyer Z., Wu T. Y., Davis M. R., Chandler D. C., Weisburd B., Houlden H., Reilly M. M., Laing N. G., Lamont P. J., Roxburgh R. H., Ravenscroft G. (2020). A novel RFC1 repeat motif (ACAGG) in two Asia-Pacific CANVAS families. BRAIN (ONLINE), vol. 143, p. 2904- 2910, ISSN: 1460-2156, doi: 10.1093/brain/awaa263 University of Sydney Kumar K. R*., Cortese A*., Tomlinson S. E., Efthymiou S., Ellis M., Zhu D., Stoll M., Dominik N., Tisch S., Tchan M., Wu K. H. C., Devery S., Spring P. J., Hawke S., Cremer P., Ng K., Reilly M. M., Nicholson G. A., Houlden H., Kennerson M. (2020). RFC1 expansions can mimic hereditary sensory neuropathy with cough and Sjögren syndrome. BRAIN (ONLINE), vol. 143, p. e82, ISSN: 1460-2156, doi: 10.1093/brain/awaa244 University of Tubingen and collaborators of ARCA consortium Traschütz A, Cortese A, Reich S, Dominik N, Faber J, Jacobi H, Hartmann AM, Rujescu D, Montaut S, Echaniz-Laguna A, Erer S, Schütz VC, Tarnutzer AA, Sturm M, Haack TB, Vaucamps-Diedhiou N, Puccio H, Schöls L, Klockgether T, van de Warrenburg BP, Paucar M, Timmann D, Hilgers RD, Gazulla J, Strupp M, Moris G, Filla A, Houlden H, Anheim M, Infante J, Basak AN, Synofzik M; RFC1 Study Group.Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1 Disease. Neurology. 2021 Mar 2;96(9):e1369-e1382. doi: 10.1212/WNL.0000000000011528. Epub 2021 Jan 25. Paris - Pitie'-Salpetriere Cortese A., Tozza S., Yau W. Y., Rossi S., Beecroft S. J., Jaunmuktane Z., Dyer Z., Ravenscroft G., Lamont P. J., Mossman S., Chancellor A., Maisonobe T., Pereon Y., Cauquil C., Colnaghi S., Mallucci [...] H., Houlden H., Reilly M. M. (2020). Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion. BRAIN, vol. 143, p. 489-490, ISSN: 0006-8950, doi: 10.1093/brain/awz418 |
Start Year | 2020 |
Description | Genotype and phenotype spectrum of RFC1 CANVAS and disease spectrum |
Organisation | University of Perth |
Country | Australia |
Sector | Academic/University |
PI Contribution | As stated in the project proposal, we partnered with several centres around the world to fully define the genotype and phenotype spectrum RFC1 disease. We have tested over the last year over 2000 samples with ataxia and/or sensory neuropathy for RFC1 expansion sent to us from all across the world, as shown in the research output. Identification of novel population specific pathogenic configuration in RFC1 |
Collaborator Contribution | Contribution with patients samples and clinical information. |
Impact | University of Perth Beecroft S. J., Cortese A., Sullivan R., Yau W. Y., Dyer Z., Wu T. Y., Mulroy E., Pelosi L., Rodrigues M., Taylor R., Mossman S., Leadbetter R., Cleland J.,Anderson T., Ravenscroft G., Laing N. G., Houlden H., Reilly M. M., Roxburgh R. H. (2020). A Maori specific RFC1 pathogenic repeat configuration in CANVAS, likely due to a founder allele. BRAIN (ONLINE), vol. 143, p. 2673-2680, ISSN: 1460-2156, doi: 10.1093/brain/awaa203 Scriba C. K., Beecroft S. J., Clayton J. S., Cortese A., Sullivan R., Yau W. Y., Dominik N., Rodrigues M., Walker E., Dyer Z., Wu T. Y., Davis M. R., Chandler D. C., Weisburd B., Houlden H., Reilly M. M., Laing N. G., Lamont P. J., Roxburgh R. H., Ravenscroft G. (2020). A novel RFC1 repeat motif (ACAGG) in two Asia-Pacific CANVAS families. BRAIN (ONLINE), vol. 143, p. 2904- 2910, ISSN: 1460-2156, doi: 10.1093/brain/awaa263 University of Sydney Kumar K. R*., Cortese A*., Tomlinson S. E., Efthymiou S., Ellis M., Zhu D., Stoll M., Dominik N., Tisch S., Tchan M., Wu K. H. C., Devery S., Spring P. J., Hawke S., Cremer P., Ng K., Reilly M. M., Nicholson G. A., Houlden H., Kennerson M. (2020). RFC1 expansions can mimic hereditary sensory neuropathy with cough and Sjögren syndrome. BRAIN (ONLINE), vol. 143, p. e82, ISSN: 1460-2156, doi: 10.1093/brain/awaa244 University of Tubingen and collaborators of ARCA consortium Traschütz A, Cortese A, Reich S, Dominik N, Faber J, Jacobi H, Hartmann AM, Rujescu D, Montaut S, Echaniz-Laguna A, Erer S, Schütz VC, Tarnutzer AA, Sturm M, Haack TB, Vaucamps-Diedhiou N, Puccio H, Schöls L, Klockgether T, van de Warrenburg BP, Paucar M, Timmann D, Hilgers RD, Gazulla J, Strupp M, Moris G, Filla A, Houlden H, Anheim M, Infante J, Basak AN, Synofzik M; RFC1 Study Group.Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1 Disease. Neurology. 2021 Mar 2;96(9):e1369-e1382. doi: 10.1212/WNL.0000000000011528. Epub 2021 Jan 25. Paris - Pitie'-Salpetriere Cortese A., Tozza S., Yau W. Y., Rossi S., Beecroft S. J., Jaunmuktane Z., Dyer Z., Ravenscroft G., Lamont P. J., Mossman S., Chancellor A., Maisonobe T., Pereon Y., Cauquil C., Colnaghi S., Mallucci [...] H., Houlden H., Reilly M. M. (2020). Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion. BRAIN, vol. 143, p. 489-490, ISSN: 0006-8950, doi: 10.1093/brain/awz418 |
Start Year | 2020 |
Description | Genotype and phenotype spectrum of RFC1 CANVAS and disease spectrum |
Organisation | University of Sydney |
Country | Australia |
Sector | Academic/University |
PI Contribution | As stated in the project proposal, we partnered with several centres around the world to fully define the genotype and phenotype spectrum RFC1 disease. We have tested over the last year over 2000 samples with ataxia and/or sensory neuropathy for RFC1 expansion sent to us from all across the world, as shown in the research output. Identification of novel population specific pathogenic configuration in RFC1 |
Collaborator Contribution | Contribution with patients samples and clinical information. |
Impact | University of Perth Beecroft S. J., Cortese A., Sullivan R., Yau W. Y., Dyer Z., Wu T. Y., Mulroy E., Pelosi L., Rodrigues M., Taylor R., Mossman S., Leadbetter R., Cleland J.,Anderson T., Ravenscroft G., Laing N. G., Houlden H., Reilly M. M., Roxburgh R. H. (2020). A Maori specific RFC1 pathogenic repeat configuration in CANVAS, likely due to a founder allele. BRAIN (ONLINE), vol. 143, p. 2673-2680, ISSN: 1460-2156, doi: 10.1093/brain/awaa203 Scriba C. K., Beecroft S. J., Clayton J. S., Cortese A., Sullivan R., Yau W. Y., Dominik N., Rodrigues M., Walker E., Dyer Z., Wu T. Y., Davis M. R., Chandler D. C., Weisburd B., Houlden H., Reilly M. M., Laing N. G., Lamont P. J., Roxburgh R. H., Ravenscroft G. (2020). A novel RFC1 repeat motif (ACAGG) in two Asia-Pacific CANVAS families. BRAIN (ONLINE), vol. 143, p. 2904- 2910, ISSN: 1460-2156, doi: 10.1093/brain/awaa263 University of Sydney Kumar K. R*., Cortese A*., Tomlinson S. E., Efthymiou S., Ellis M., Zhu D., Stoll M., Dominik N., Tisch S., Tchan M., Wu K. H. C., Devery S., Spring P. J., Hawke S., Cremer P., Ng K., Reilly M. M., Nicholson G. A., Houlden H., Kennerson M. (2020). RFC1 expansions can mimic hereditary sensory neuropathy with cough and Sjögren syndrome. BRAIN (ONLINE), vol. 143, p. e82, ISSN: 1460-2156, doi: 10.1093/brain/awaa244 University of Tubingen and collaborators of ARCA consortium Traschütz A, Cortese A, Reich S, Dominik N, Faber J, Jacobi H, Hartmann AM, Rujescu D, Montaut S, Echaniz-Laguna A, Erer S, Schütz VC, Tarnutzer AA, Sturm M, Haack TB, Vaucamps-Diedhiou N, Puccio H, Schöls L, Klockgether T, van de Warrenburg BP, Paucar M, Timmann D, Hilgers RD, Gazulla J, Strupp M, Moris G, Filla A, Houlden H, Anheim M, Infante J, Basak AN, Synofzik M; RFC1 Study Group.Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1 Disease. Neurology. 2021 Mar 2;96(9):e1369-e1382. doi: 10.1212/WNL.0000000000011528. Epub 2021 Jan 25. Paris - Pitie'-Salpetriere Cortese A., Tozza S., Yau W. Y., Rossi S., Beecroft S. J., Jaunmuktane Z., Dyer Z., Ravenscroft G., Lamont P. J., Mossman S., Chancellor A., Maisonobe T., Pereon Y., Cauquil C., Colnaghi S., Mallucci [...] H., Houlden H., Reilly M. M. (2020). Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion. BRAIN, vol. 143, p. 489-490, ISSN: 0006-8950, doi: 10.1093/brain/awz418 |
Start Year | 2020 |
Description | Natural history of SORD neuropathy |
Organisation | University of Miami |
Country | United States |
Sector | Academic/University |
PI Contribution | Enrolment of cases from UK and Europe. testing of sorbitol level |
Collaborator Contribution | Enrolment of cases from USA |
Impact | Final analysis of data. Manuscript will be submitted in 2023. Preliminary data were presented during the PNS 2023 |
Start Year | 2020 |
Description | Visiting fellow Arianna Ghia |
Organisation | University of Pavia |
Country | Italy |
Sector | Academic/University |
PI Contribution | hosting a visiting medical student |
Collaborator Contribution | University of Pavia allowed the student to spend a year working on her medical thesis. The student also obtained indepedent funding from CARIPLO foundation to cover her expenses |
Impact | MD thesis |
Start Year | 2023 |
Description | Visiting research fellow (Elisa Vegezzi) |
Organisation | University of Pavia |
Country | Italy |
Sector | Academic/University |
PI Contribution | Elisa Vegezzi has been awarded an EJP RD ERN RD Research Mobility Fellowship to work on long read sequencing at UCL ION under my supervision |
Collaborator Contribution | Elisa will be contributing with samples and will help with long read sequencing. She is also leading on a review paper on novel non-coding repeat expansion diseases |
Impact | Review "Neurological disorders caused by novel non-coding repeat expansions: clinical, genetic, and molecular features" Vegezzi E / Cortese A under review |
Start Year | 2023 |
Description | Visiting research fellow (Riccardo Curro) |
Organisation | University of Pavia |
Country | Italy |
Sector | Academic/University |
PI Contribution | Trainee neurologist (Dr Riccardo Curro') awarded with EAN training fellowship visiting the lab for 1 year and working on the MRC project. Training on clinical and lab techniques. He later decided to stay, funded by University of Pavia (Italy), to complete part of his PhD to the modelling and functional investigation of disease mechanism in RFC1 disease using IPSC neuron models. |
Collaborator Contribution | Carrying our clinical and lab research on RFC1 expansion disease. Modelling of RFC1 disease using IPSC neurons |
Impact | Truncating Variants in RFC1 in Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome. Ronco R, Perini C, Currò R, Dominik N, Facchini S, Gennari A, Simone R, Stuart S, Nagy S, Vegezzi E, Quartesan I, El-Saddig A, Lavin T, Tucci A, Szymura A, Novis De Farias LE, Gary A, Delfeld M, Kandikatla P, Niu N, Tawde S, Shaw J, Polke J, Reilly MM, Wood NW, Crespan E, Gomez C, Chen JYH, Schmahmann JD, Gosal D, Houlden H, Das S, Cortese A. Neurology. 2023 Jan 31;100(5):e543-e554. doi: 10.1212/WNL.0000000000201486. Epub 2022 Oct 26. PMID: 36289003 Free PMC article. The first two-year follow-up in a patient with isolated sensory neuronopathy due to biallelic expansion in RFC1 gene. Tozza S, Currò R, Severi D, Marcelli V, Cavaliere C, Esposito G, Iodice R, Cortese A, Manganelli F. Acta Neurol Belg. 2022 Oct 10. doi: 10.1007/s13760-022-02116-7. Online ahead of print. PMID: 36214978 No abstract available. Severe distinct dysautonomia in RFC1-related disease associated with Parkinsonism. Record CJ, Alsukhni RA, Curro R, Kaski D, Rubin JS, Morris HR, Cortese A, Iodice V, Reilly MM. J Peripher Nerv Syst. 2022 Dec;27(4):311-315. doi: 10.1111/jns.12515. Epub 2022 Oct 7. PMID: 36177974 Exploratory analysis of lower limb muscle MRI in a case series of patients with SORD neuropathy. O'Donnell LF, Cortese A, Rossor AM, Laura M, Blake J, Skorupinska M, Lunn MP, Thornton JS, Currò R, Morrow JM, Reilly MM. J Neurol Neurosurg Psychiatry. 2022 Jul 22:jnnp-2022-329432. doi: 10.1136/jnnp-2022-329432. Online ahead of print. PMID: 35868853 No abstract available. Unusual upper limb features in SORD neuropathy. Record CJ, Pipis M, Blake J, Curro R, Lunn MP, Rossor AM, Laura M, Cortese A, Reilly MM. J Peripher Nerv Syst. 2022 Jun;27(2):175-177. doi: 10.1111/jns.12492. Epub 2022 Apr 13. PMID: 35419909 No abstract available. Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS): genetic and clinical aspects. Cortese A, Curro' R, Vegezzi E, Yau WY, Houlden H, Reilly MM. Pract Neurol. 2022 Feb;22(1):14-18. doi: 10.1136/practneurol-2020-002822. Epub 2021 Aug 13. PMID: 34389644 Review. RFC1 expansions are a common cause of idiopathic sensory neuropathy. Currò R, Salvalaggio A, Tozza S, Gemelli C, Dominik N, Galassi Deforie V, Magrinelli F, Castellani F, Vegezzi E, Businaro P, Callegari I, Pichiecchio A, Cosentino G, Alfonsi E, Marchioni E, Colnaghi S, Gana S, Valente EM, Tassorelli C, Efthymiou S, Facchini S, Carr A, Laura M, Rossor AM, Manji H, Lunn MP, Pegoraro E, Santoro L, Grandis M, Bellone E, Beauchamp NJ, Hadjivassiliou M, Kaski D, Bronstein AM, Houlden H, Reilly MM, Mandich P, Schenone A, Manganelli F, Briani C, Cortese A. Brain. 2021 Jun 22;144(5):1542-1550. doi: 10.1093/brain/awab072. |
Start Year | 2020 |
Title | TREATMENT AND DETECTION OF INHERITED NEUROPATHIES AND ASSOCIATED DISORDERS |
Description | The present disclosure relates to methods of detecting and treating inherited neuropathy. In various aspects, the method comprises detecting the presence of a mutation in the sorbitol dehydrogenase (SORD) gene in a sample from a subject. In various embodiments, th SORD mutation is a DNA variant classified as pathogenic or likely pathogenic according to American College of Medical Genetics and Genomics (ACMG) criteria. |
IP Reference | WO2020227430 |
Protection | Patent / Patent application |
Year Protection Granted | 2020 |
Licensed | Commercial In Confidence |
Impact | Potential treatment of patients with SORD neuropathy with aldose reductase inhibitors. |
Title | Pharmacodynamic EffIcacy and Clinical Benefit of AT 007 in Patients With Sorbitol Dehydrogenase (SORD) Deficiency (INSPIRE) |
Description | This international, multi-center, randomized, double-blinded, placebo-controlled, phase 2-3 study is designed to assess the pharmacodynamic (PD) efficacy and clinical benefit of long term administration of AT 007 versus placebo in male and non-pregnant female subjects with genetically confirmed SORD Deficiency aged 18-55 and able to ambulate with a 10MWRT time of <10 seconds. The study will be conducted at up to 12 sites worldwide. Genetically confirmed SORD Deficiency patients with blood sorbitol levels >10,000 ng/ml will be screened and randomized in a 2:1 ratio to receive either AT-007 daily or a matching placebo for 24 months. A total of up to 72 subjects will be enrolled. The primary clinical outcome measure, 10-meter walk-run test (10MWRT), will be assessed at 24 months and compared to baseline. |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Late clinical evaluation |
Year Development Stage Completed | 2023 |
Development Status | Under active development/distribution |
Impact | phase 3 trial ongoing, which started only 2 years after the identification of SORD gene as a common cause of inherited neuropathy (Cortese A, Nature Genetics, 2020) |
URL | https://clinicaltrials.gov/ct2/show/NCT05397665 |
Description | Invited Seminar during the 5th Asian Oceanic Inherited Neuropathy Consortium (AOINC) Virtual Symposium- Friday 13 November 2020- 10 am - 12.30 pm. Title:'Repeats and retrogenes: novel hidden causes of inherited neuropathies" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Neurologists, paediatricians, researchers from several countries in East Asia and Oceania attended the meeting. Raised awareness of recent findings and novel causes of neuropathy. Fostering identification of patients with potentially treatable SORD neuropathy. Plans for collaborative studies including clinicians from developing countries |
Year(s) Of Engagement Activity | 2020 |
URL | http://asianoceanicinc.org/wp-content/uploads/2020/10/Virtual-AOINC-Symposium-Program_FINAL-2020-11-... |
Description | Invited speaker to the 3rd Brazilian Conference of Neurogenetics |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | I was invited to give two talks " Explaining the hidden heritability of peripheral neuropathies" and "One gene, many phenotypes: the RFC1 tale". Also I was part of a roundtable discussion "My personal view on the future of neurogenetics in the next 5 - 10 years" |
Year(s) Of Engagement Activity | 2023 |
URL | https://congressobrasileirodeneurogenetica.com/ |
Description | Invited talk on novel technologies in neurogenetics, Minisimposium, Peripheral Nerve Society, Copenhagen |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited talk on novel technologies in neurogenetics, Minisimposium, Peripheral Nerve Society, Copenhagen. over 100 people attended the symposium and reported interest and increased awareness of novel technologies available to investigate genetics of unsolved cases |
Year(s) Of Engagement Activity | 2024 |
Description | Member of expert panel of ClinGen - CMT working group. ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building a central resource that defines the clinical relevance of genes and variants for use in precision medicine and research. |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Member of expert panel of ClinGen - CMT working group. ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building a central resource that defines the clinical relevance of genes and variants for use in precision medicine and research. The activity involved bi-monthly meeting when the panel of experts review evidence to support pathogenicity of genes and variants causing CMT and |
Year(s) Of Engagement Activity | 2022,2023 |
URL | https://clinicalgenome.org/ |
Description | NAF zoom meetings to engage the patient population "Research and Drug Development for CANVAS" |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | zoom meeting to engage the patient population diagnosed with RFC1 CANVAS. Provide update on research and management as answer questions. Webinar was recorded and available on youtube |
Year(s) Of Engagement Activity | 2024 |
URL | https://www.youtube.com/watch?v=IcKmKEEhZA8 |
Description | Neurology Grand Rounds at the University of Michigan |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | I was invited to present at the Neurology Grand Rounds at the University of Michigan. Talk "Repeat expansions and retrogenes: novel hidden causes of inherited neurological disease" |
Year(s) Of Engagement Activity | 2022 |
Description | New, frequent and increasing numbers of repeat expansion disorders in neurology" a 6th Congress of the European Academy of Neurology - 1st Virtual Congress 23 - 26 May 2020. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Educational course on recently identified repeat expansion. The course was well attended and received positive feedback. Audience reported change in view, fostering identification of cases and providing more patients with a genetic diagnosis. |
Year(s) Of Engagement Activity | 2020 |
URL | https://www.ean.org/congress-2020 |
Description | invited talk during the American Academy of Neurology 2020. "recessive repeat expansion causes CANVAS and is a common cause of Late-Onset Sensory Ataxia" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited seminar on the recently identified RFC1 repeat expansion. The virtual event was well attended and received positive feedback. Audience reported change in view, fostering identification of cases and providing more patients with a genetic diagnosis. |
Year(s) Of Engagement Activity | 2020 |
Description | invited talk during the American Academy of Neurology 2021. "Biallelic mutations in SORD are a common cause of potentially treatable genetic neuropathy" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited seminar on the recently identified SORD neuropathy. The virtual event was well attended and received positive feedback. Audience reported change in view, fostering identification of cases and providing more patients with a genetic diagnosis. |
Year(s) Of Engagement Activity | 2021 |
Description | invited talk during the Italian Peripheral nerve society meeting (ASNP) held in Milano, November 2021. Title: "Repeat expansions and retrogenes: novel hidden causes of inherited neuropathies" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Invited seminar on the novel causes of inherited neuropathy. The virtual event was well attended and received positive feedback. Audience reported change in view, fostering identification of cases and providing more patients with a genetic diagnosis. |
Year(s) Of Engagement Activity | 2021 |