A de novo mutation of the MYH7 gene in a large Chinese family with autosomal dominant myopathy

Laing distal myopathy (LDM) is an autosomal dominant myopathy that is caused by mutations in the slow/beta cardiac myosin heavy-chain (MYH7) gene. It has been recently reported that LDM presents with a wide range of clinical manifestations. We herein report a large Chinese family with autosomal dominant myopathy. The affected individuals in the family presented with foot drop in early childhood, along with progressive distal and proximal limb weakness. Their characteristic symptoms include scapular winging and scoliosis in the early disease phase and impairment of ambulation in the advanced phase. Although limb-girdle muscle dystrophy (LGMD) was suspected initially, a definite diagnosis could not be reached. As such, we performed linkage analysis and detected four linkage regions, namely 1q23.2-24.1, 14q11.2-12, 15q26.2-26.3 and 17q24.3. Through subsequent whole exome sequencing, we found a de novo p.K1617del causative mutation in the MYH7 gene and diagnosed the disease as LDM. This is the first LDM case in China. Our patients have severe clinical manifestations that mimic LGMD in comparison with the patients with the same mutation reported elsewhere. Discovery of a mutation in a skeletal muscle gene has revealed the first case of Laing distal myopathy (LDM) ever reported in China. Tatsushi Toda at the Kobe University Graduate School of Medicine and coworkers in Japan and China were studying a muscular disorder that occurred in 14 of 52 members of one family, across 5 generations. Patients showed severe spinal twisting in childhood and slow, progressive weakening of the limbs as they aged. The researchers initially suspected limb girdle muscle dystrophy, but genetic analysis revealed a deletion in MYH7, a gene that encodes slow/beta cardiac myosin heavy chain, a protein found in fatigue-resistant, slow-twitch, skeletal muscle fibers. This deletion is diagnostic of LDM. The symptoms and severity of LDM may vary greatly, and screening for MYH7 mutations may help to identify undiagnosed cases.