Dataset Information

Identification of a New Mutation (L46P) in the Human NOG Gene in an Italian Patient with Symphalangism Syndrome.

ABSTRACT: Proximal symphalangism (SYM1) is a joint morphogenesis disorder characterized by stapes ankylosis, proximal interphalangeal joint fusion, skeletal anomalies and conductive hearing loss. Noggin is a bone morphogenetic protein (BMP) antagonist essential for normal bone and joint development in humans and mice. Autosomal dominant mutations have been described in the NOG gene, encoding the noggin protein. We analyzed an Italian sporadic patient with SYM1 due to a novel NOG mutation (L46P) based on a c.137T>C transition. A different pathogenic mutation in the same codon (L46D) has been previously described in an in vivo chicken model. An in silico model shows a decreased binding affinity between noggin and BMP7 for both L46D and L46P compared to the wild type. Therefore, this codon should play an important role in BMP7 binding activity of the noggin protein and consequently to the joint morphogenesis.

SUBMITTER: Athanasakis E

PROVIDER: S-EPMC3398819 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Identification of a New Mutation (L46P) in the Human NOG Gene in an Italian Patient with Symphalangism Syndrome.

Athanasakis E E Biarnés X X Bonati M T MT Gasparini P P Faletra F F

Molecular syndromology 20120411 1

Proximal symphalangism (SYM1) is a joint morphogenesis disorder characterized by stapes ankylosis, proximal interphalangeal joint fusion, skeletal anomalies and conductive hearing loss. Noggin is a bone morphogenetic protein (BMP) antagonist essential for normal bone and joint development in humans and mice. Autosomal dominant mutations have been described in the NOG gene, encoding the noggin protein. We analyzed an Italian sporadic patient with SYM1 due to a novel NOG mutation (L46P) based on a ...[more]

PMID: 22855651

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Project description:BackgroundProximal symphalangism (SYM1) is a rare genetic bone disorder characterized by the fusion of proximal interphalangeal joints in the hands and feet. Genetic studies have identified two genes underlying SYM1 as the noggin (NOG) and the growth differentiation factor 5 (GDF5).Case reportIn the present report, a 43-year-old gravida at 11 weeks of gestation was referred for evaluation of abnormal fusions of the joints. In the initial diagnosis, physical examination was undertaken. However, traditional radiological examination was not applied due to the need to protect the fetus, making diagnosis results inefficient to determine the exact disease affecting the proband. To acquire alternative clinical evidences, we conducted radiological examinations on two other affected family members. The radiological examination revealed that they carried the symphalangism accompanied with tarsal coalition, a very rare manifestation of SYM1. A combination of whole exome sequencing (WES) and Sanger sequencing revealed a novel heterozygous missense mutation (c.163G > T; p.Asp55Tyr) in the NOG gene, which could be associated with the observed pathogenic SYM1 in the studied family. The p.Asp55Tyr mutation co-segregated with SYM1 through the affected and unaffected family members. In silico structural modeling of the p.Asp55Tyr mutation showed that it abolishes the interaction with the Arg167 residue and causes a change in the electrostatic potential profile of the type II binding site of the noggin protein.ConclusionOur findings indicate that the genetic test based on WES can be useful in diagnosing SYM1 patients, with particular advantages in preventing the fetus from contacting harmful X-ray through the traditional radiography. The novel pathogenic mutation identified would further expand our understanding of the mutation spectrum of NOG in association with SYM1 disease and provide a guidance on how to determine whether the fetus is affected by SYM1 through the prenatal diagnosis.

Dataset Information

Identification of a New Mutation (L46P) in the Human NOG Gene in an Italian Patient with Symphalangism Syndrome.

Publications

Identification of a New Mutation (L46P) in the Human NOG Gene in an Italian Patient with Symphalangism Syndrome.

Similar Datasets

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