Novel NOG (p.P42S) mutation causes proximal symphalangism in a four-generation Chinese family

BACKGROUND: Proximal symphalangism (SYM1; OMIM 185800), also called Cushing’s symphalangism, is an infrequent autosomal dominant disease. An SYM1 patient typically features variable fusion of proximal interphalangeal joints in the hands and feet. METHODS: We recruited a four-generation Chinese non-consanguineous family with SYM1. We examined their hands and feet using X-rays to confirm fusion of proximal interphalangeal joints. We evaluated their audiology using standard audiometric procedures and equipment. Then, we identified genetic variants using whole exome sequencing and validated mutations using Sanger sequencing. Mutation pathogenicity was analyzed with bioinformatics. RESULTS: Radiographs revealed proximal-joint fusion of fingers and toes in the patients. Two elderly individuals (II:1 and II:4) exhibited slight hearing loss. Additionally, we detected a novel heterozygous missense mutation in exon 1 of NOG (NM_005450) c.124C > T, p.(Pro42Ser) in all patients. This c.124C > T mutation is highly conserved across multiple species and the p.(Pro42Ser) variation is potentially highly pathogenic. CONCLUSION: Our results suggest that heterozygous c.124C > T, p.(Pro42Ser) in NOG is a novel mutation that causes human SYM1 phenotype. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12881-019-0864-1) contains supplementary material, which is available to authorized users.