Facio-scapulo-humeral muscular dystrophy (FSH) is characterized by a relaxation of chromatin as well as a decrease (hypomethylation) of DNA in the D4Z4 region of chromosome 4, causing the expression of the DUX4 gene which codes for the eponymous transcription factor.
Two forms of FSH:
- type 1 FSH (in 95% of cases) linked to a decrease in the number of repetitions of D4Z4 sequence ;
- type 2 FSH (FSH2) linked to abnomalities in SMCHD1 gene, on chromosome 18 or to abnomalities in DNMT3B gene on chromosome 20.
By examining the muscle biopsy and the genetic profile of a patient with FSH2, the team of S. van der Maarel identified an abnormality in the LRIF1 gene on chromosome 1. The LRIF1 gene codes for a protein known to interact with SMCHD1 : they both play a role in the inactivation of the X chromosome in women by promoting the compaction of chromatin.
In this patient, the abnormality of the identified LRIF1 gene leads to a relaxation of the chromatin and the expression of DUX4 and the proteins it activates, which is the origin of an authentic form of FSH2.
