New Facioscapulohumeral Muscular Dystrophy Test Identifies Key Epigenetic Signature

A new study entitled “Identifying diagnostic DNA methylation profiles for facioscapulohumeral muscular dystrophy in blood and saliva using bisulfite sequencing” published in the Clinical Epigenetics journal designed an assay that identifies the epigenetic signature for both types of Facioscapulohumeral muscular dystrophy from a multiple collections of samples, including blood or saliva.

Facioscapulohumeral muscular dystrophy (FSHD) is typically identified before the age of 20, and is characterized by weakness of face muscles, stabilizers of the scapula or the dorsiflexors of the foot. While patients’ life expectancy is not affected, approximately 20% of patients will need a wheelchair. The disease is caused, most likely, by abnormal expression of a gene – double homeobox-containing gene (Dux4) — in muscle cells. The gene, localized at chromosome 4q35, in affected individuals is shortened, leading to chromatin relaxation due to epigenetic modifications. Diagnosis relies on complex molecular genetic testing. While facioscapulohumeral muscular dystrophy 1 (FSHD1) is diagnosed by identifying shortening of the D4Z4 allele below 11 repeats (normal alleles have 11 to 100 repeat units), FSHD2 patients exhibit chromatin relaxation at D4Z4 independent of D4Z4 contraction, thus cannot be identified by standard FSHD1 genetic testing. However, both forms are associated with epigenetic alterations, such as DNA methylation.

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In this study, the authors developed a PCR-based assay to identify changes in DNA methylation and postulated that these alterations could identify and distinguish both forms of FSHD. To establish their strategy, they analyzed samples from both healthy controls, and patients clinically diagnosed with FSHD, both FSHD1 and FSHD2. They found DNA hypomethylation was restricted to FSHD1 patients, when compared to healthy controls that were identified as hypermethylated. FSHD2 patients exhibited extremely DNA hypomethylation profile.

The new developed assay is suggested by the authors as an efficient and rapid new method to identify and distinguish FSHD1 and FSHD2 patients and can be applied to samples, from cultured cells or tissue samples to blood and saliva.