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Analysis of TGFBI gene mutations in Chinese patients with corneal dystrophies and review of the literature.

ABSTRACT: PURPOSE: To analyze human transforming growth factor b-induced (TGFBI) gene mutations in Chinese patients with corneal dystrophies (CDs). METHODS: Twenty-one families with corneal dystrophies were subjected to phenotypic and genotypic characterization. The corneal phenotypes of patients were documented by slit lamp photography. Mutation screening of the coding regions of TGFBI was performed by direct sequencing. An additional 43 families and 3 sporadic patients with TGFBI dystrophies from China reported in the literature were reviewed. RESULTS: Five mutations of TGFBI were identified in 21 families with CDs, including one novel small deletion mutation, c.delta1838-1849 (p.Delta613-616VAEP), responsible for one variant lattice CD (LCD) family and 4 known mutations, R555W mutation for 10 granular cornea dystrophy type I (GCD1) families, R124H for 5 GCD type II (GCD2), R124C for 4 LCD1, and H626R for one variant LCD. In a cohort of Chinese patients (n=355) with TGFBI dystrophies from 64 families and 3 sporadic cases, 19 distinct mutations were found in several different CD subtypes. The 3 most common phenotypes were ranked as follows: GCD1, GCD2, and LCD1. Mutation hot spots at R124 and R555 occurred in >80% of these families. CONCLUSIONS: Our findings extend the mutational spectrum of TFGBI, and this is also the first extensively delineated TGFBI mutation profile associated with the various corneal dystrophies in the Chinese population.

SUBMITTER: Yang J

PROVIDER: S-EPMC2901189 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Analysis of TGFBI gene mutations in Chinese patients with corneal dystrophies and review of the literature.

Yang Juhua J Han Xiaoli X Huang Dinggou D Yu Lin L Zhu Yihua Y Tong Yi Y Zhu Binliang B Li Chuanbao C Weng Mingshe M Ma Xu X

Molecular vision 20100630

<h4>Purpose</h4>To analyze human transforming growth factor b-induced (TGFBI) gene mutations in Chinese patients with corneal dystrophies (CDs).<h4>Methods</h4>Twenty-one families with corneal dystrophies were subjected to phenotypic and genotypic characterization. The corneal phenotypes of patients were documented by slit lamp photography. Mutation screening of the coding regions of TGFBI was performed by direct sequencing. An additional 43 families and 3 sporadic patients with TGFBI dystrophie ...[more]

PMID: 20664689

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Project description:PURPOSE: To screen a cohort of corneal dystrophy patients from North India for mutations in the transforming growth factor beta induced (TGFBI) gene, to correlate genotypes to phenotypes, to describe structural implications of various mutations on protein function, and to discuss the implications for diagnosis. METHODS: Eighty affected individuals from 61 unrelated families, who were diagnosed with autosomal dominant granular and/or lattice corneal dystrophy, were recruited for the study. Detailed clinical evaluation was undertaken for these patients to establish their corneal phenotypes. Genomic DNA was isolated from peripheral blood samples and all exons of TGFBI were screened for mutations by polymerase chain reaction (PCR) and direct DNA sequencing. Protein molecular dynamics (MD) simulations were performed for the mutations detected to assess the changes in protein structure. RESULTS: The most common mutations seen were Arg555Trp and Arg124Cys. Two novel mutations, Ser516Arg (c.DNA1548C>G), with a phenotype similar to granular corneal dystrophy I (GCDI), and Leu559Val (c.DNA1675T>G), with an atypical phenotype closely resembling epithelial basement membrane dystrophy/map dot fingerprint dystrophy, were identified. Protein modeling studies involving wild type and mutant protein indicated that the Leu559Val is a destabilizing mutation and that Ser516Arg could adversely affect the specific binding of Fas1 domain 4 with other proteins. In addition, two single-nucleotide polymorphisms, rs4669 and rs11331170, were also identified. Mutations were not identified in 8 affected individuals, 6 of whom were diagnosed with bowman layer dystrophy and 2 with lattice corneal dystrophy. CONCLUSIONS: This is the first comprehensive report of TGFBI mutations covering a large part of North India. Identification of novel mutations, the presence of phenotypic variability, and the genetic heterogeneity seen in our cases stress the need for mandatory screening of TGFBI for precise diagnosis and classification of corneal dystrophies.

Dataset Information

Analysis of TGFBI gene mutations in Chinese patients with corneal dystrophies and review of the literature.

Publications

Analysis of TGFBI gene mutations in Chinese patients with corneal dystrophies and review of the literature.

Similar Datasets

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