Proximal symphalangism (SYM1) is an autosomal dominant disorder, mainly characterized by variable fusion of the proximal interphalangeal joints of the hands and feet To date, two genes, GDF5 and NOG, have been reported to associate with SYM1. Herein, we clinically characterized a Chinese family with fusions of the bilateral proximal interphalangeal joints in the 2-5 digits without conductive hearing loss. Direct DNA sequencing of the two genes revealed a novel heterozygous missense mutation (c.499C>T, p.R167C) in the NOG gene. This mutation co-segregates with the phenotype in the family and is not present in the 200 control individuals. The cA99C>T mutation is predicted to change the conserved amino acid arginine at codon 167 to cysteine at the protein level. A different mutation in the same codon (R167G) has been described to cause brachydactyly type B2 (BDB2). Our work indicates that the cA99C>T (R167C) mutation is likely to represent the pathogenic mutation in the family. This finding broadens the spectrum of NOG mutations associated with SYM1 and will help to provide genetic counseling to the affected family. (C) 2013 Elsevier B.V. All rights reserved.
[1]Huazhong Univ Sci & Technol, Key Lab Mol Biophys, Ctr Human Genome Res, Minist Educ,Coll Life Sci & Technol, Wuhan 430074, Hubei, Peoples R China.
[2]Hubei Polytech Inst, Hebei 432000, Peoples R China.
[3]Fudan Univ, Sch Life Sci, Shanghai 200433, Peoples R China.
[4]Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Wuhan 430022, Hubei, Peoples R China.
[5]Xiaogan Cent Hosp, Xiaogan 432000, Hubei, Peoples R China.
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