Digenic Inheritance of Shortened Repeat Units of the D4Z4 Region and a Loss-of-Function Variant in SMCHD1 in a Family With FSHD.

ABSTRACT: Facioscapulohumeral muscular dystrophy (FSHD) is a neuromuscular disorder which is typically transmitted by an autosomal dominant pattern, although reduced penetrance and sporadic cases caused by de novo mutations, are often observed. FSHD may be caused by a contraction of a repetitive element, located on chromosome 4 (4q35). This locus is named D4Z4 and consists of 11 to more than 100 repeated units (RU). The D4Z4 is normally hypermethylated and the genes located on this locus are silenced. In case of FSHD, the D4Z4 region is characterized by 1-10 repeats and results in the region being hypomethylated. However, 5% of FSHD cases do not carry the short allele of D4Z4 region. To date, two forms of FSHD (FSHD1 and FSHD2) are known. FSHD2 is usually observed in patients without the D4Z4 fragme

SUBMITTER: Cascella R 

PROVIDER: S-EPMC6279899 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature