A Heterozygous Mutation in the Filamin C Gene Causes an Unusual Nemaline Myopathy With Ring Fibers

Teresinha Evangelista (1, 2) , Xavière Lornage (3) , Pierre Carlier (1) , Guillaume Bassez (1, 2) , Guy Brochier (1, 2) , Anaïs Chanut (1) , Emmanuelle Lacène (1, 2) , Mai-Thao Bui (1) , Corinne Metay (2, 2) , Ursula Oppermann (3) , Johann Böhm (3) , Jocelyn Laporte (3) , Norma Romero (1, 2)

1 Institut de Myologie
2 CHU Pitié-Salpêtrière [AP-HP]
3 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire

Autosomal dominant pathogenic variants in the filamin C gene (FLNC) have been associated with myofibrillar myopathies, distal myopathies, and isolated cardiomyopathies. Mutations in different functional domains of FLNC can cause various clinical phenotypes. A novel heterozygous missense variant c.608G>A, p.(Cys203Tyr) in the actin binding domain of FLCN was found to cause an upper limb distal myopathy (MIM #614065). The muscle MRI findings are similar to those observed in FLNC-myofibrillar myopathy (MIM #609524). However, the muscle biopsy revealed >20% of muscle fibers with nemaline bodies, in addition to numerous ring fibers and a predominance of type 1 fibers. Overall, this case shows some unique and rare aspects of FLNC-myopathy constituting a new morphologic phenotype of FLNC-related myopathies.

Mots clés: Filamin C (FLNC); Filamin C-related myopathies; Muscle MRI; Nemaline bodies; Sarcomere disorganization

Domaines: Neurosciences [q-bio.NC]

Teresinha Evangelista, Xavière Lornage, Pierre Carlier, Guillaume Bassez, Guy Brochier, et al.. A Heterozygous Mutation in the Filamin C Gene Causes an Unusual Nemaline Myopathy With Ring Fibers. Journal of Neurology, Neurosurgery and Psychiatry, 2020, 79 (8), pp.908-914. ⟨10.1093/jnen/nlaa052⟩. ⟨hal-03664347⟩