Molecular diagnostics of FSHD remains complex for approximately 20% of patients, posing difficulties in genetic counseling. To overcome these current limitations, we have developed a molecular combing-based method allowing a precise bar coding of the 4q35 locus linked to the disease and 10qter region, which is highly homologous. By exploring a thousand cases with this approach, we have increased FSHD diagnostic rate and identified atypical genomic features in more than 7% of patients.

Our work highlights the heterogeneous molecular signature of FSHD and the difficulty of interpretation of the molecular data in a significant proportion of cases, especially for genetic counseling, predictive testing or prenatal diagnosis. (By Dr. Frederique Magdinier, https://jmg.bmj.com/content/early/2019/04/22/jmedgenet-2018-105949 )