Investigation of the molecular aspects of growth and development

Lead Research Organisation: St George's University of London
Department Name: Basic Medical Sciences

Abstract

Poor growth is a relatively common problem in early childhood and in certain cases is known to be associated in the long term with an increased risk of medical problems including learning difficulties, diabetes, heart disease and certain types of cancer. In many cases the underlying cause is unknown. A significant contribution to our understanding of the processes involved in growth and development has come from the study of diseases that are rare in the general population but occur more frequently in isolated communities. Genes are the way that we store our hereditary information. These communities have the advantage that they have inherited the disease causing gene from a common ancestor making it far easier for scientists to identify it. The fellow will study two rare syndromes in the Amish community; a key component of each condition is insufficient growth. The aim will be to identify the disease causing gene(s) and to study their function. We hypothesise that analyzing the function of these genes will help us understand more about disorders of human growth which arise when the molecules involved do not function properly.

Technical Summary

Disorders causing growth insufficiency are common in early childhood. Poor growth particularly during fetal development and early infancy is associated with an increased risk of morbidity. In the majority of cases the aetiological basis remains unidentified.

Two distinct disorders that result in growth failure have been identified in the Amish community. The first is microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1) which is characterised by poor prenatal growth and subsequent postnatal growth restriction, microcephaly, dysmorphic facial features and specific skeletal abnormalities. The second condition appears to be new to medical science and is characterised by cerebral aneurysms, short stature and hoarse voice (ASH syndrome). Using extensive family cohorts we undertook a genome-wide high density SNP microarray study in affected and unaffected family members which led to the identification of novel gene loci for each condition; a ~3Mb region on chromosome 2 (MOPD), and a ~5.4Mb region on chromosome 20 (ASH syndrome).

This project aims to discover the genes and mutations responsible for these conditions, and investigate the molecular processes perturbed by these aberrations. We will use next generation sequencing technologies to undertake whole-exome sequence analysis of affected cases and verify the causative mutations by cosegregation and regional/non-region (non-Amish) control analysis, and investigate the causative (MOPD1) gene identified in other cases of primordial dwarfism. Following identification of the causative genetic variant(s) the study will be extended to tissue distribution analysis, protein localisation studies and pathway analysis.

The discovery of the causative genetic variants in these syndromes will make a significant contribution to our understanding of the molecular processes involved in growth and development. There is potential here to identify novel disease mechanisms and pathways involved in this important area. Additionally this study presents a rare opportunity to clinically characterise a novel disorder of growth and development namely ASH syndrome.

Publications

10 25 50
 
Description A community approach to accelerate the discovery of the molecular basis of neurodevelopmental disorders
Amount £100,000 (GBP)
Funding ID 209083/Z/17/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2017 
End 01/2019
 
Description Alexander Fleming Dissemination Award
Amount £30,000 (GBP)
Funding ID C0486 
Organisation Medical Research Council (MRC) 
Department Medical Research Foundation
Sector Charity/Non Profit
Country United Kingdom
Start 06/2014 
End 06/2015
 
Description Alexander Fleming Dissemination Award
Amount £30,000 (GBP)
Funding ID MRF-145-0003-DG-BAPLE 
Organisation Medical Research Council (MRC) 
Department Medical Research Foundation
Sector Charity/Non Profit
Country United Kingdom
Start 03/2017 
End 03/2018
 
Description Alexander Fleming dissemination award
Amount £30,000 (GBP)
Funding ID MRF-145-0001-DG-BAPLE 
Organisation Medical Research Council (MRC) 
Department Medical Research Foundation
Sector Charity/Non Profit
Country United Kingdom
Start 10/2015 
End 09/2016
 
Description Confidence in concept
Amount £26,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 12/2016 
End 05/2017
 
Description Medical Research Foundation - Alexander Fleming Dissemination Award (Invited)
Amount £30,000 (GBP)
Funding ID MRF-145-0005-DG-BAPLE 
Organisation Medical Research Council (MRC) 
Department Medical Research Foundation
Sector Charity/Non Profit
Country United Kingdom
Start 03/2018 
End 03/2019
 
Description Newlife Foundation for Disabled Children, Project Grant
Amount £119,999 (GBP)
Funding ID 16-17/12 
Organisation Newlife 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2017 
End 05/2018
 
Description Project grant
Amount £511,890 (GBP)
Funding ID MR/L006812/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 02/2014 
End 02/2017
 
Description Project grant
Amount $1,900,000 (USD)
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start  
 
Description St George's University of London MRC centenary fund award
Amount £14,150 (GBP)
Organisation St George's University of London 
Sector Academic/University
Country United Kingdom
Start  
 
Title Windows of Hope database 
Description The "Windows of Hope" project website houses a searchable database of gene cards for all known inherited disorders identified within the Anabaptist (Amish/Mennonite) communities. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact This database which is updated to reflect new scientific and clinical knowledge is widely used by clinicians, genetic counsellors, healthcare workers, teachers and academics serving/working with the Anabaptist communities as an information source to aid their clinical practice. The disorders identified within the Amish community occur worldwide and clinicians and academics working with families affected by or studying rare inherited monogenic disorders also access this site, providing a channel to develop new scientific collaborations and improving diagnostic rates and clinical management for patients with rare genetic disorders. 
URL https://wohproject.com/
 
Description Baylor College of Medicine 
Organisation Baylor College of Medicine
Department Department of Molecular and Human Genetics
Country United States 
Sector Academic/University 
PI Contribution Shared data exchange and resources for next generation sequencing
Collaborator Contribution Shared data exchange and resources for next generation sequencing
Impact Multidisciplinary genomic research with Dr Jim Lupski (Genomics) and Peggy Goodall (molecular biology). Manuscript publications: PMID: 30158690, PMID: 30157172, PMID: 28334956
Start Year 2015
 
Description Dr Jose Luis Rosa (HERC2) 
Organisation University of Barcelona
Department Department of Physiological Sciences II
Country Spain 
Sector Academic/University 
PI Contribution Disease gene identification and phenotype delineation for an Angelman-like condition present at high frequency amongst the Amish.
Collaborator Contribution Investigation of specific functional aspects of the gene involved
Impact Manuscript: Mutation of HERC2 causes developmental delay with Angelman-like features. Journal of Medical Genetics, PMID: 23243086; PMID: 27528230
Start Year 2011
 
Description Dr Michael Kessels (KPTN) 
Organisation University Hospital Jena
Country Germany 
Sector Hospitals 
PI Contribution Disease gene discovery and clinical delineation of a novel neurodevelopmental disorder with macrocephaly (PMID: 24239382)
Collaborator Contribution Investigation of specific functional aspects of the gene involved
Impact Mutations in KPTN cause macrocephaly, neurodevelopmental delay, and seizures, American Journal of Human Genetics, PMID: 24239382
Start Year 2013
 
Description Dr Scheffner (HERC2) 
Organisation University of Konstanz
Department Konstanz Research School Chemical Biology
Country Germany 
Sector Academic/University 
PI Contribution Disease gene identification and phenotype delineation for an Angelman-like condition present at high frequency amongst the Amish.
Collaborator Contribution Investigation of specific functional aspects of the gene involved.
Impact Manuscript - Mutation of HERC2 causes developmental delay with Angelman-like features. Journal of Medical Genetics, PMID: 23243086
Start Year 2011
 
Description FutureLearn 
Organisation FutureLearn Limited
PI Contribution Development of the educational materials for Massive Open Online Course (MOOC) "Genomic Medicine and Research: A Community Approach" This includes video and audio recordings of interviews with Amish families, clinicians and special educational needs providers undertaken for the course
Collaborator Contribution Platform provider for the MOOC
Impact https://www.futurelearn.com/your-programs (please note the course is not yet open for registration)
Start Year 2018
 
Description Galloway-Mowat syndrome 
Organisation Dalhousie University
Department Department of Biology
Country Canada 
Sector Academic/University 
PI Contribution Clinical studies and disease gene discovery for Galloway-Mowat syndrome, alongside specific functional studies of the molecules involved
Collaborator Contribution Phenotype description, disease gene identification, specific functional studies
Impact Publication of manuscript, PMID: 26070982, Development of diagnostic testing, Family support group meeting, ESHG young investigator award,
Start Year 2013
 
Description KPTN mouse model 
Organisation The Wellcome Trust Sanger Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Detailed delineation of the genetic basis of the human KPTN disorder and correlation with the mouse model
Collaborator Contribution Generation of KPTN model and in depth phenotyping and downstream molecular analysis
Impact Multi-disciplinary collaboration with Prof Matthew Hurles and Dr Sebastian Gerety to investigate the KPTN mouse and correlate phenotypic outcomes with those associated with the human disorder
Start Year 2013
 
Description New Leaf Center clinic for special children 
Organisation New Leaf Center Clinic for Special Children
Country United States 
Sector Hospitals 
PI Contribution 1. Jointly held Akron Children's Hospital IRB: : Improving diagnosis, clinical outcome, and molecular understanding of inherited conditions in the Anabaptist community. 2. Jointly organise disease specific family days, attended by families in the Ohio area affected by genetic disorders. Our team supports community and family liaison, coordination of the events, generates practical educational materials for the families and facilitates the family discussions. 3. Jointly develop disease specific and community sensitive literature for families and primary and specialist health and educational workers. . 4. In partnership with Dr Olivia Wenger and her colleagues at the New Leaf Center clinic for special children, through jointly organised research clinics we undertake immediately translational patient focused research. These studies have led to significantly improved diagnostic rates and clinical management for Amish families affected by genetic disorders and contributed to the development of reduced cost local CLIA diagnostic services for the conditions we have identified and clinically characterised. 5. Funding for a clinical research coordinator based full time at New Leaf clinic.
Collaborator Contribution Jointly held IRB: : Improving diagnosis, clinical outcome, and molecular understanding of inherited conditions in the Anabaptist community. Jointly run family disease specific information days Jointly designed disease specific information leaflets for families and healthcare workers Coordinate collaborative research clinics
Impact Jointly run family disease specific information days Jointly designed disease specific information leaflets for families and healthcare workers. Publication of manuscript, PMID: 26070982. NORD patient information: https://rarediseases.org/rare-diseases/galloway-mowat-syndrome/
Start Year 2011
 
Description PlexSeq diagnostics 
Organisation PlexSeq Diagnostics
PI Contribution Joint development of a diagnostic platform with the capability to provide community specific genetic newborn screening and carrier testing for the Amish community. Conceived the concept of this platform after careful consultation with the Amish community and local and specialists clinicians working with affected families. Utilising our knowledge of the spectrum and nature of genetic disorders affecting the Amish community, we provided the information regarding the genetic variants to be included in the test design. Our research team are developing the assay to extract high quality DNA from dried blood spots and validating the diagnostic platform.
Collaborator Contribution Joint development of a diagnostic platform with the capability to provide community specific genetic newborn screening and carrier testing for the Amish community. PleqSeq contributed technical expertise, staff and reagent costs to enable development of the testing platform.
Impact Joint development of a diagnostic platform with the capability to provide community specific genetic newborn screening and carrier testing for the Amish community, currently undergoing technical validation. Manuscript submitted to the European Journal of Human Genetics on work related to this collaboration, currently under revision. A further manuscript is currently being finalised for submission to the American Journal of Medical Genetics.
Start Year 2016
 
Description Prof Alan Lehmann (PCNA) 
Organisation University of Sussex
Department Genome Damage and Stability Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution Disease gene identification, phenotype delineation and specific functional studies for a novel disorder resulting from dysfunctional DNA repair.
Collaborator Contribution Generation of human cell lines. Immortalisation of cell lines. Functional studies. Scientific support.
Impact Manuscript publication PMID: 24911150; PMID: 25485490
Start Year 2011
 
Description Prof Andrew Jackson (PCNA/DNMT3A) 
Organisation Medical Research Council (MRC)
Department MRC Human Genetics Unit
Country United Kingdom 
Sector Public 
PI Contribution Disease gene identification, phenotype delineation and protein function studies for a novel disorder resulting from dysfunctional DNA repair (PCNA). Exploration of the epigenetic outcomes resulting from DNMT3A loss of function variants.
Collaborator Contribution Extensive primordial dwarfism cohort screened for novel disease genes on site, consumables and sequencing costs were provided by the collaborator. Clinical and scientific support for the PCNA and DNMT3A studies.
Impact Multidisciplinary collaboration with Prof Andrew Jackson and colleagues at the MRC Human Genetics Unit in Edinburgh, to undertake genetic and functional studies. Published manuscript: Hypomorphic PCNA mutation underlies a human DNA repair disorder, Journal of Clinical Investigation, PMID: 24911150; PMID: 26641461
Start Year 2011
 
Description Prof Catherine Green (PCNA) 
Organisation University of Oxford
Department Wellcome Trust Centre for Human Genetics
Country United Kingdom 
Sector Academic/University 
PI Contribution Disease gene identification, phenotype delineation and for a novel disorder resulting from dysfunctional DNA repair. Co-applicant on a successful MRC grant awarded December 2013.
Collaborator Contribution Scientific support and investigation of specific functional aspects of the gene involved.
Impact PMID: 24911150; PMID: 25485490; PMID: 28073635 MRC project grant: Molecular and cellular characterisation of an important new DNA repair disorder (awarded Dec 2013)
Start Year 2011
 
Description Prof Fowzan Alkuraya 
Organisation King Fahad Specialist Hospital
PI Contribution We work closely with Prof Alkuraya as part of an international program to define new causes of inherited neurological and ocular conditions. We provide expert genetic/genomic analyses to define new causes of inherited disease as part of our community genomic research studies.
Collaborator Contribution We work closely with Prof Alkuraya as part of an international program to define new causes of inherited neurological and ocular conditions. We provide expert genetic/genomic analyses to define new causes of inherited disease as part of our community genomic research studies.
Impact Manuscript publication: PMID: 28081210
Start Year 2015
 
Description Prof Ken Campellone) WHAMM/WDR73 
Organisation University of Connecticut
Department Department of Molecular and Cell Biology
Country United States 
Sector Academic/University 
PI Contribution Genetic, clinical and functional studies identifying the molecular basis of Galloway Mowat syndrome
Collaborator Contribution Functional studies of the gene and mutation identified
Impact Co-Applicant on NIH grant funding, MRC Centenary Award funding (to Emma Baple), European Society of Human Genetics Young Investigator Award (to Emma Baple) based on the WDR73 disease gene discovery, Publications: PMID: 26070982; PMID: 28720660
Start Year 2012
 
Description The La Farge Medical Clinic (The Center for Special Children) 
Organisation La Farge Medical Clinic
Department Center for Special Children
Country United States 
Sector Hospitals 
PI Contribution 1. Jointly organised CME accredited educational symposium (Practical Approaches to Inherited Disease in the Plain Communities in Wisconsin). Alongside conceiving the symposium, planning, funding, administration and community and healthcare worker liaison, our team gave practical clinically focused presentations and chaired sessions. The longstanding relationship we have established with the community has enabled us to collate a unique clinical educational resource comprising of audiovisual materials that illustrate the clinical features of disorders identified within the Amish community. We provided access to these materials for speakers at the event to use for their presentations. Feedback illustrated the invaluable nature of such clinical resources, which will lead to improved recognition and understanding, diagnostics, counselling and clinical management for these disorders, ultimately leading to improved healthcare outcomes for affected families. We also contributed to the extensive clinically focused educational materials generated for symposium attendees. 2. Jointly organised a Troyer syndrome family day, attended by families in the Wisconsin area affected by Troyer syndrome. Our team supported community and family liaison, coordination of the event, generated practical educational materials for the family and facilitated the family discussions. 3. In partnership with Dr Jim Deline and his colleagues at the La Farge Clinic Center for Special Children through jointly organised research clinics we undertake immediately translational patient focused research. These studies have led to significantly improved diagnostic rates and clinical management for Amish families affected by genetic disorders and contributed to the development of reduced cost local CLIA diagnostic services for the conditions we have identified and clinically characterised.
Collaborator Contribution 1. Jointly organised CME accredited educational symposium (Practical Approaches to Inherited Disease in the Plain Communities in Wisconsin) October 22nd 2016. The event was held at the University of Wisconsin which enabled CME credits and Midwifery Continuing Education Credits to be provided for attendees. Clinicians and other healthcare workers from the University of Wisconsin were involved in the organisation and administration of the event, chaired educational sessions, developed educational materials and gave clinically focused presentations. 2. Jointly organised a Troyer syndrome family day, attended by families in the Wisconsin area affected by Troyer syndrome. The event was held at one of the families homes and also attended by a speech and language therapist, occupational therapist and physical therapist from the University of Wisconsin as well as clinicians from the La Farge Medical Clinic. 3. Clinical and scientific collaborative input enabling clinical characterisation and identification of the molecular basis of inherited disorders occurring within the Wisconsin Amish community.
Impact Practical Approaches to Inherited Disease in the Plain Communities in Wisconsin symposium (http://events.r20.constantcontact.com/register/event?oeidk=a07ed5hfhgd17ecf8bb«r=4phnt6dab)
Start Year 2013
 
Description University of Wisconsin 
Organisation University of Wisconsin-Madison
Department Genetics
Country United States 
Sector Academic/University 
PI Contribution 1. Jointly organised CME accredited educational symposium (Practical Approaches to Inherited Disease in the Plain Communities in Wisconsin). Alongside conceiving the symposium, planning, funding, administration and community and healthcare worker liaison, our team gave practical clinically focused presentations and chaired sessions. The longstanding relationship we have established with the community has enabled us to collate a unique clinical educational resource comprising of audiovisual materials that illustrate the clinical features of disorders identified within the Amish community. We provided access to these materials for speakers at the event to use for their presentations. Feedback illustrated the invaluable nature of such clinical resources, which will lead to improved recognition and understanding, diagnostics, counselling and clinical management for these disorders, ultimately leading to improved healthcare outcomes for affected families. We also contributed to the extensive clinically focused educational materials generated for symposium attendees. 2. Jointly organised a Troyer syndrome family day, attended by families in the Wisconsin area affected by Troyer syndrome. Our team supported community and family liaison, coordination of the event, generated practical educational materials for the family and facilitated the family discussions. 3. In partnership with the University of Wisconsin clinicians, we undertake immediately translational patient focused research in collaboration with the University of Wisconsin. These studies have led to improved diagnostic rates and clinical management for Amish families affected by genetic disorders and contributed to the development of reduced cost local CLIA diagnostic services for the conditions we have identified and clinically characterised. 4. Development of a genotyping platform with PlexSeq diagnostics to support carrier and newborn testing in the Wisconsin State Laboratory of Hygiene.
Collaborator Contribution 1. Jointly organised CME accredited educational symposium (Practical Approaches to Inherited Disease in the Plain Communities in Wisconsin) October 22nd 2016. The event was held at the University of Wisconsin which enabled CME credits and Midwifery Continuing Education Credits to be provided for attendees. Clinicians and other healthcare workers from the University of Wisconsin were involved in the organisation and administration of the event, chaired educational sessions, developed educational materials and gave clinically focused presentations. 2. Jointly organised a Troyer syndrome family day, attended by families in the Wisconsin area affected by Troyer syndrome. The event was held at one of the families homes and also attended by a speech and language therapist, occupational therapist and physical therapist from the University of Wisconsin as well as clinicians from the La Farge Medical Clinic. 3. Clinical and scientific collaborative input enabling clinical characterisation and identification of the molecular basis of inherited disorders occurring within the Wisconsin Amish community. 4. CLIA laboratory support for development of a new genotyping platform to support carrier and newborn testing for the Amish community
Impact Multidisciplinary translational collaborative genomic and clinical research with Prof Mei Baker, Prof Christine Seroogy, Dr Jess Scott-Schwoerer, Dr Katie Williams and Dr Greg Rice. We have jointly organised a CME accredited educational symposium (Practical Approaches to Inherited Disease in the Plain Communities in Wisconsin) and developed a genotyping platform with PlexSeq diagnostics to support diagnostic (CLIA) carrier and newborn testing for the Amish community.
Start Year 2015
 
Title Amish Genotyping Platform 
Description MRC confidence in concept funding to the University of Exeter 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Initial development
Year Development Stage Completed 2018
Development Status Under active development/distribution
Impact Developed collaborations with PlexSeq diagnostics and the Wisconsin State Laboratory of Hygiene 
 
Description 5th Annual Translational Medicine in the Plain Populations Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk and session chair to update health care workers, patients and their families and the wider Amish community on the progress made in understanding inherited diseases. Participation in the GM3 synthase deficiency working group
Year(s) Of Engagement Activity 2017
URL http://www.chp.edu/our-services/rare-disease-therapy/news-events/translational-medicine
 
Description A talk or presentation - 6th Annual Translational Medicine in the Plain Populations Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited platform presentation at the annual Plain Communities Translational Medicine Conference. Asked to discuss the advantages of genomic data sharing and also took part in disease specific workshops. The event was attended by around 100 academics, health care workers, Amish and Mennonite families and community leaders. The discussions at this conference have led to collaboration with the Wisconsin State Laboratory of Hygiene to further develop a genotyping platform to provide this as a diagnostic (CLIA) test.
Year(s) Of Engagement Activity 2018
URL https://www.waisman.wisc.edu/event/plain-conference-2018/
 
Description Amish and Mennonite family meeting for developmental disorder 
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 Family meeting for Amish and Mennonite families affected by a developmental disorder.
Families from Ohio, Pennsylvania, Canada, Indiana and Wisconsin attended and shared their experiences of the disorder.
Updates on research results were shared with the families and all those not currently enrolled in the study asked to be enrolled.
Families shared contact details.
Year(s) Of Engagement Activity 2016
 
Description Educational meeting for lay and registered Midwives 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Midwife educational meeting held on the 22nd September 2017 to improve knowledge and understanding of inherited disorder within the Amish communities and the benefits of newborn screening. The meeting was attended by lay and registered midwives
Year(s) Of Engagement Activity 2017
 
Description Educational meeting with CME credits: Practical Approaches to Amish Inherited Disease 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The conference (educational meeting) was designed for clinicians and other health care workers, educators, administrators and board members who serve the Anabaptist (Amish and Mennonite) populations west of central Pennsylvania. Title of the event: Practical Approaches to Amish Inherited Disease.
Over 100 attendees. Speakers from across the USA contributed.
CME credits were awarded by Akron Children's Hospital and Ohio Board of Nursing for CEU credits.
The event was funded by the MRF Alexander Fleming Dissemination Award Scheme.
Feedback was all extremely positive and a further dissemination award has been given to hold a similar event in Wisconsin this year.
Year(s) Of Engagement Activity 2015
URL https://cmetracker.net/CHMCA/Files/Brochures/3330.pdf
 
Description Family support meetings for Amish inherited disorders 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact Talks sparked many questions from families and discussion.

The families and wider Amish community supported our application for an Alexander Fleming Dissemination Award by writing letters to the funding body for inclusion with the application form.
Year(s) Of Engagement Activity 2011,2012,2013,2014,2015
 
Description GM3 synthase deficiency family meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact Family meeting and working group to discuss and strategise the approach to management of GM3 and GM2 synthase deficiency. The event was held at the clinic for special children on 18 May 2017 and was attended by affected families, clinicians, academics and pharmaceutical companies with an interest in ganglioside disorders and developing management strategies and therapies for this group of diseases. Gave a short talk aimed at families describing what is known about GM2 synthase deficiency. The working group identified research priorities and discussed defining an agreed clinical management strategy. The work of this group is still ongoing.
Year(s) Of Engagement Activity 2017
 
Description Grand Round Akron Children's Hospital - Think Global, Practice Local: Community Genetics in Amish Country 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Participation in Medical Grand Round presentation to educate paediatricians serving the Ohio Amish community about the presentation, diagnosis and management of inherited paediatric disorders enriched within the community
Year(s) Of Engagement Activity 2018
URL https://cmetracker.net/CHMCA/Archive?
 
Description Information meeting for families with children in inherited neurodevelopmental disorder 
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 Meeting for Amish families with children affected by a complex developmental disorder. The meeting was jointly organised with New Leaf Center clinic for special children, Ohio and the Community Health Clinic, Indiana.
Families from Ohio, Indiana and Wisconsin attended as well as clinicians, dieticians, nurses and special educational needs workers caring for Amish children.
Families were given updates regarding research progress and new knowledge about the disorder. A new research study to learn more about the disorder was launched and all the families that attended chose to participate.
Several people asked if there could be a similar meeting every year. The families decided to start a circle letter.
Feedback included: "best day ever", "this was a lifesaver for my daughter as meeting other families means she does not feel so alone"
Year(s) Of Engagement Activity 2016
 
Description New Leaf Centre Newletter 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact Newsletters describing the immediately translational impacts of embedding research within the clinical setting
Year(s) Of Engagement Activity 2015,2016,2017
URL http://newleafclinic.org/newsletters/
 
Description Practical Approaches to Inherited Disease in the Plain Communities in Wisconsin - CME accredited 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Educational symposium attended by around 100 family doctors, hospital clinicians, midwives, Amish lay midwives, health care workers, educators, administrators and board members who serve the Plain (Amish and Mennonite) populations in Wisconsin. The meeting was accredited for CME and also nursing and midwifery CEU credits.
Attendees reported that what they had learnt would change their practice, feedback was exemplary.
There was increased interest in our research studies and new collaborations were formed.
Year(s) Of Engagement Activity 2016
URL http://events.r20.constantcontact.com/register/event?oeidk=a07ed5hfhgd17ecf8bb&llr=4phnt6dab
 
Description Situs Inversus and PCD family meetings 
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 Held two family meetings for Amish and Mennonite families affected by Situs Inversus/Primary Ciliary Dyskinesia to share research findings, answer questions, recruit additional participants and plan further studies. Families from Canada and across the USA attended.
Year(s) Of Engagement Activity 2018
 
Description SpringHaven meeting 
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 Information meeting to provide updates on to Amish and Mennonite families affected or at risk of a complex neurodevelopmental disorder. Local heathcare workers and supporters of the research study were also invited and attended.
A question and answer session was very successful. All questions were provided anonymously on cards to encourage involvement without embarrassment.
Very positive feedback.
Year(s) Of Engagement Activity 2016
 
Description Transient Neonatal Study Day 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact Invited medical representative, transient neonatal diabetes patient study day held at SOAS in London - attended by patients and scientific and medical experts in the field of imprinting disorders and neonatal diabetes.
Sparked discussion with patients and scientific experts.

Continued Collaboration with Professor Karen Temple and Dr Deborah Mackay, Human Genetics, University of Southampton
Year(s) Of Engagement Activity 2011
 
Description Translational Medicine in the Plain Populations conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation to healthcare workers, clinical researchers, Amish leaders and affected families. The purpose of the talk was to discuss genomic data sharing to improve healthcare outcomes for Amish and Mennonite families with rare inherited disorders.
Year(s) Of Engagement Activity 2016
URL http://www.indianachc.org/wp/fourth_annual_conference/
 
Description Troyer Syndrome family meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact On 23rd October 2017, we jointly organised a Troyer syndrome family day with the University of Wisconsin and La Farge clinic Center for Special Children, attended by families in the Wisconsin and Ohio regions affected by Troyer syndrome. The event was held at one of the families homes and also attended by a speech and language therapist, occupational therapist and physical therapist from the University of Wisconsin as well as clinicians from the La Farge Medical Clinic. We shared updates on our research studies with the families and the therapists provided practical information and support. The families were provided with culturally sensitive educational materials about the disorder. The discussions with the families has led to a collaborative natural history study to address their questions about disease progression, prognosis and management.
Year(s) Of Engagement Activity 2017
 
Description Walking with giants support group meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact Invited medical representative, walking with giants patient support group meeting held in Liverpool. Attended by patients and their families, medical and scientific experts in the field of primordial dwarfism.

Led to continued collaboration with Dr Andrew Jackson, MRC Human Genetics Unit, University of Edinburgh.
Year(s) Of Engagement Activity 2011
 
Description Walsh College seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation to local medical students and other healthcare workers
Year(s) Of Engagement Activity 2016