- Between 2009 and 2018, whole exome sequencing of 310 families affected by congenital myopathy as part of the MYOCAPTURE project, supported by the AFM-Téléthon, identified 14 new genes:
- four linked to other neuromuscular diseases or cardiomyopathy (ASCC1, HSPB8, CACNA1S, MYPN),
- ten never implicated in a genetic neuromuscular disease (ACTN2, CASQ1, GGPS1, MAP3K20/ZAK, ORAI1, MYO18B, PYROXD1, SRPK3, STIM1 and UNC45B)
- Nearly two-thirds had centronuclear myopathy (26%), core myopathy (17%), nemalin myopathy (13%) or tubular aggregate myopathy (10%).
- Lâanomalie gĂ©nĂ©tique en cause a Ă©tĂ© identifiĂ©e dans 50% des cas avec un diagnostic foThe genetic anomaly in question was identified in 50% of cases, with a formal diagnosis in 40% of cases, the remaining 10% being linked to a variant in a candidate gene which the absence of samples from related individuals meant could not be confirmed by segregation analyses.
- Thirty-six per cent of the resolved cases had a known gene with a corresponding phenotype, while 44% were atypical for the gene in question.
- New genes implicated in congenital myopathy accounted for 20% of resolved cases.
- The diagnostic yield was 48% when the genome of three family members was analysed, compared with 29% when exome sequencing involved only two.
- Muscle biopsy also helped to improve the genetic diagnosis, since the variant in question was identified in 42% of families with a biopsy, compared with 14% of families where no muscle biopsy was available.
Exome sequencing in undiagnosed congenital myopathy reveals new genes and refines genes-phenotypes correlations. de Feraudy Y, Vandroux M, Romero NB et al. Genome Med. 2024 Jul 9;16(1):87.
