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

• Published in: Journal of neuropathology and experimental neurology Vol. 79; no. 8; pp. 908 - 914
• Main Authors: Evangelista, Teresinha, Lornage, Xavière, Carlier, Pierre G, Bassez, Guillaume, Brochier, Guy, Chanut, Anais, Lacène, Emmanuelle, Bui, Mai-Thao, Metay, Corinne, Oppermann, Ursula, Böhm, Johann, Laporte, Jocelyn, Romero, Norma B
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.08.2020; by American Association of Neuropathologists, Inc
• Subjects: Adult; Causes of; Development and progression; Female; Filamins - genetics; Gene mutations; Genetic aspects; Heterozygosis; Heterozygosity; Heterozygote; Humans; Male; Medical research; Medicine, Experimental; Middle Aged; Mutation; Myopathies, Nemaline - genetics; Myopathies, Nemaline - pathology; Myopathies, Structural, Congenital - genetics; Myopathies, Structural, Congenital - pathology; Neuromuscular diseases; Pedigree; Phenotype; France; Sarcomere disorganization; Filamin C (FLNC); Nemaline bodies; Filamin C-related myopathies; Muscle MRI
• ISSN: 0022-3069; 1554-6578; 1554-6578
• DOI: 10.1093/jnen/nlaa052

Abstract 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.