A new homozygous missense variant in LMOD3 gene causing mild nemaline myopathy with prominent facial weakness.

Nemaline myopathy (NEM) type 10, caused by biallelic mutations in LMOD3, is a severe congenital myopathy clinically characterized by generalized hypotonia and muscle weakness, respiratory insufficiency, joint contractures, and bulbar weakness. Here, we describe a family with two adult patients presenting mild nemaline myopathy due to a novel homozygous missense variant in LMOD3. Both patients presented mild delayed motor milestones, frequent falls during infancy, prominent facial weakness and mild muscle weakness in the four limbs. Muscle biopsy showed mild myopathic changes and small nemaline bodies in a few fibers. A neuromuscular gene panel revealed a homozygous missense variant in LMOD3 that co-segregated with the disease in the family (NM_198271.4: c.1030C>T; p.Arg344Trp). The patients described here provide evidence of the phenotype-genotype correlation, suggesting that non-truncating variants in LMOD3 lead to milder phenotypes of NEM type 10.

Association of fingerprint bodies with rods in a case with mutations in the LMOD3 gene.

Fingerprint bodies are observed in a variety of clinical situations with no definite genetic cause identified so far. We report for the first time the association of fingerprint bodies with rods in a patient who developed a slowly progressive myopathy affecting the face and limb extremities. Ultrastructural examination first disclosed fingerprint bodies and on a second biopsy, associated cytoplasmic bodies and rods. Next Generation Sequencing panel of congenital nemaline myopathy genes allowed the identification of two novel variants, a deleterious missense variant (c.1628G>T, p.Arg543Leu) located in the WASP-homology 2 domain, and a deletion (c.366delG, p.Lys122AsnFs*6) in the LMOD3 gene, generally causing severe nemaline myopathy with antenatal onset and early death. Recently, a less severe phenotype similar to our case has been reported. Our study confirms the existence of milder phenotypes linked to LMOD3 mutations and underlines that fingerprint bodies, though not specific, may be an early ultrastructural marker that could be linked, among others, to nemaline myopathy.