Methylation studies to help with the molecular diagnosis of FSHD

The Italian consortium dedicated to facioscapulohumeral muscular dystrophy (FSHD) reports on its experience in integrating methylation studies into the routine diagnosis of this myopathy with an excessively complex pathophysiology:

• 218 patients with or suspected of having FSHD were included in the study,
• in addition to measuring the number of D4Z4 repeats and 4qA/B haplotyping, methylation was specifically studied in two critical areas of the D4Z4 locusPosition d’un gène dans le génome. Le locus d’un gène est désigné par le numéro du chromosome, le bras du chromosome, puis sa place. Par exemple le gène de la maladie de Duchenne est sur le locus Xp21, ce qui veut dire qu’il est sur le locus 21 du bras court (p) du chromosome X., namely DUX4-PAS and DR1,
• the sensitivity and specificity of the test were found to be very acceptable,
• the test enabled confirmation of the diagnosis of FSHD (FSHD1 or FSHD2), even in pre- or pauci-symptomatic individuals.

This work once again highlights the importance of epigenetic factors in FSHD.

Integrating D4Z4 methylation analysis into clinical practice: improvement of FSHD molecular diagnosis through distinct thresholds for 4qA/4qA and 4qA/4qB patients. Strafella C, Megalizzi D, Trastulli G, et al. Clin Epigenetics. 2024 Oct.