Distal arthrogryposis (DA) type 2B (DA2B) is an autosomal dominant congenital disorder, characterized by camptodactyly, thumb adduction, ulnar deviation and facial features, including small mouth, down‑slanting palpebral fissure and slight nasolabial fold. It has been reported that four genes are associated with DA2B, including troponin I, fast‑twitch skeletal muscle isoform, troponin T3, fast skeletal, myosin heavy chain 3 (MYH3) and tropomyosin 2, which are all associated with embryonic limb morphogenesis and skeletal muscle contraction. In the present study, three affected family members and five unaffected individuals were identified through clinical and radiological assessment. Genomic DNA was obtained from the three patients, which then underwent whole‑exome sequencing, and candidate mutations were verified by Sanger sequencing in all available family members and 100 healthy volunteers. Then, the spatial models of embryonic MYH were further constructed. In the clinic, the three patients recruited to the present study were diagnosed with DA2B. Mutation analysis indicated that there was a novel heterogeneous missense mutation c.2506 A>G (p.K836E) in the MYH3 gene among the affected individuals, which was highly conserved and was not identified in the unaffected family members and healthy controls. Furthermore, protein modeling revealed that the altered position interacted with regulatory light chain. Thus, the present study identified a novel pathogenic mutation of the MYH3 gene in a Chinese family with DA2B, which expanded the mutational spectrum of MYH3 and provided additional information regarding the association between mutation locations and different types of DA.
Keywords: myosin heavy chain 3; distal arthrogryposis type 2B; embryonic myosin heavy chain; mutation.