Hypomethylation is restricted to the D4Z4 repeat array in phenotypic FSHD.

Area of Science:

• Genetics
• Epigenetics
• Molecular Biology

Background:

• Facioscapulohumeral muscular dystrophy (FSHD) is linked to D4Z4 repeat array contraction and hypomethylation on chromosome 4q.
• D4Z4 hypomethylation is also present in phenotypic FSHD without contraction and in ICF syndrome, a distinct genetic disorder.

Purpose of the Study:

• To investigate epigenetic and genetic commonalities/differences between phenotypic FSHD and ICF syndrome.
• To identify the gene defect and pathogenetic epigenetic pathway in phenotypic FSHD.

Main Methods:

• DNA methylation analysis of non-D4Z4 repeat arrays.
• Lymphocyte analysis for pericentromeric abnormalities (chromosomes 1, 9, 16).
• Immunoglobulin level determination (IgA, IgG, IgM).
• Mutational analysis of candidate genes.

Main Results:

• No epigenetic or phenotypic commonalities were found between phenotypic FSHD and ICF, apart from D4Z4 hypomethylation.
• No mutations were identified in the tested candidate genes.

Conclusions:

• In phenotypic FSHD, hypomethylation appears restricted to the D4Z4 locus.
• Phenotypic FSHD and ICF syndrome do not share a defect in the same molecular pathogenic pathway.