Update: Understanding Global Genetic Diversity in FSHD and Building International Trial Readiness

Report by Dr. Bugiardini
See also Understanding global genetic diversity in FSHD and building international trial readiness


Prof Michael Hanna (ICGNMD Director), UCL Queen Square Institute of Neurology, London, UK
Dr Stephanie Efthymiou, UCL Queen Square Institute of Neurology, London, UK
Dr Richard Lemmers & Prof Silvère van der Maarel, Leiden University Medical Centre, Leiden, The Netherlands
Dr Vishnu VY & Prof Padma Srivastava, All India Institute of Medical Sciences, Delhi, India
Dr Pedro Tomaselli & Prof Claudia Ferreira da Rosa Sobreira, FAEPA, University of Sao Paolo, Sao Paolo, Brazil

Project Overview

Our project aims to comprehensively understand global genetic diversity in Facioscapulohumeral Muscular Dystrophy (FSHD) and to build international trial readiness. The goals and objectives of the project are to investigate genetic variations associated with FSHD in different populations, assess clinical severity, and establish collaborations for potential international clinical trials.

Milestones Achieved

FAEPA cohort, Brazil (Dr Pedro Tomaselli & Prof Claudia Ferreira da Rosa Sobreira)

We successfully recruited 40 probands from Brazil with suspected clinical diagnoses of FSHD. Currently, 23 probands have been tested, and 18 of them have genetically confirmed FSHD1. Ten family members were also tested and resulted positive for FSHD1. We collected clinical data, including clinical severity and FSHD clinical scores. Initial results are promising, indicating a higher-than-expected diagnostic rate. Additional cases are being collected, and methylation analysis is ongoing.

AIIMS Cohort, India (Dr Vishnu VY & Prof Padma Srivastava)

With the support from the Indian Council of Medical Research and UCL-AIIMS Strategic Partnership, and thanks to Friends of FSH Research, we expanded the initial cohort for India and analyzed in total 91 probands with clinical symptoms consistent with FSHD. Of these, 57 cases had a 1-9U 4qA allele (Europe-based FSHD1 threshold). The FSHD1 allele size distribution in the AIIMS cohort appears intermediate between patient populations of Northeastern Asian ancestry and European ancestry. Notably, 6 asymptomatic cases had an allele of 4U or 5U, typically considered pathogenic in European populations. We observed a higher proportion of de novo participants in the AIIMS cohort (31%) and of FSHD2 cases (8%). These findings have been submitted as a research article to European Journal of Medical Genetics, and the paper has recently been accepted.

Research outputs

  • Optical Genome Mapping for the Molecular Diagnosis of Facioscapulohumeral Muscular Dystrophy: Advancement and Challenges. Ehhymiou S, Lemmers RJLF, Vishnu VY, Dominik N, Perrone B, Facchini S, Vegezzi E, Ravaglia S, Wilson L, van der Vliet PJ, Mishra R, Reyaz A, Ahmad T, Bhatia R, Polke JM, Srivastava MP, Cortese A, Houlden H, van der Maarel SM, Hanna MG, Bugiardini E. Biomolecules. 2023 Oct 24;13(11):1567. doi: 10.3390/biom13111567.

  • The first genetically confirmed cohort of Facioscapulohumeral Muscular Dystrophy from Northern India. Vishnu et al. European Journal of Human Genetics; https://doi.org/10.1038/s41431-024-01577-z

Justification for an extension

We are completing the recruitment of the Brazilian cohort and methylation analysis is in progress. We anticipate that a 6-month extension will provide the necessary time to gather data for concluding genotype-phenotype correlations in Brazil.