Genotype and phenotype analysis of 43 Iranian facioscapulohumeral muscular dystrophy patients; Evidence for anticipation

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common hereditary myopathy (prevalence 1/8300-1/20,000). It is typically characterized by progressive weakness of facial, scapular and humeral muscles. Pelvic, abdominal and lower limbs muscles may eventually be affected. FSHD is classified into two subgroups, FSHD1 and FSHD2. FSHD1 is due to a reduction in the copy number of D4Z4 macrosatellites on chromosome 4q35 (11-100 repeats in normal individuals and 1-10 repeats in patients), and FSHD2 is caused by mutations in SMCHD1 or DNMT3B. Here, we present clinical features and results of genetic analysis on 43 Iranian FSHD patients. Forty patients carried 2-7 D4Z4 repeats based on Southern blot analysis, thus confirming FSHD1 diagnosis in these patients. The number of patients with D4Z4 repeats in the range of 1-3, 4-6 and 7-9 were, respectively, 22, 17 and one. Patients with the lower number of D4Z4 repeats generally showed earlier onset and more severe disease presentations. Anticipation was observed in 14 multi-generational families. To the best of our knowledge, this is the first phenotype and genotype analysis of FSHD patients in the Iranian population. The results of this study will be beneficial for genetic counselling of FSHD patients and their families, and for the establishment of a simple affordable genetic test for Iranians as the majority of patients had 1-5 D4Z4 repeats.