Identification of a novel NOG gene mutation (P35S) in an Italian family with symphalangism

C.S.S. Mendel Institute and University La Sapienza, Rome, Italy.
Human Mutation (Impact Factor: 5.14). 03/2002; 19(3):308. DOI: 10.1002/humu.9016
Source: PubMed


Symphalangism (SYM or SYM1) is an autosomal dominant disorder characterized by multiple joint fusions. The disease is caused by mutations of the NOG gene, that maps to chromosome 17q22. So far, only six independent NOG mutations have been identified. We have analysed an Italian family in which father and son had bilateral symphalangism and detected a novel NOG mutation (P35S), originated in the father from a c.914C>T transition. A different mutation in the same codon (P35R) has been previously described. Comparison between different noggin gene hortologs shows that codon 35 is conserved. Therefore, this codon should play an important role in NOG gene function. This is the first mutation described for NOG after the initial report of NOG mutations being causative of SYM.

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    • "In addition, heterozygosity for mutations in NOGGIN has been identified in stapes ankylosis syndrome without symphalangism (MIM 184460) (Brown et al. 2002). To date, 14 distinct NOG- GIN mutations have been reported (Gong et al. 1999; Dixon et al. 2001; Takahashi et al. 2001; Brown et al. 2002; Mangino et al. 2002). The majority (10 of 14) are missense mutations, and the 4 nonsense mutations are predicted to result in premature translation termination codons. "
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