Dataset Information

Mutation survey and genotype-phenotype analysis of COL2A1 and COL11A1 genes in 16 Chinese patients with Stickler syndrome.

ABSTRACT: To identify mutations in COL2A1 and COL11A1 genes and to examine the genotype-phenotype correlation in a cohort of Chinese patients with Stickler syndrome.A total of 16 Chinese probands with Stickler syndrome were recruited, including nine with a family history of an autosomal dominant pattern and seven sporadic cases. All patients underwent full ocular and systemic examinations. Sanger sequencing was used to analyze all coding and adjacent regions of the COL2A1 and COL11A1 genes. Multiplex ligation-dependent probe amplification was performed to detect the gross indels of COL2A1 and COL11A1. Bioinformatics analysis was performed to evaluate the pathogenicity of the variants.Five mutations in COL2A1 were identified in six of 16 probands, including three novel (c.85C>T, c.3356delG, c.3401delG) mutations and two known mutations (c.1693C>T, c.2710C>T). Of the five mutations, three were truncated mutations, and the other two were missense mutations. Putative pathogenic mutations of the COL11A1 gene were absent in this cohort of patients. Gross indels were not found in COL2A1 or COL11A1 in any of the probands. High myopia was the most frequent initial ocular phenotype of Stickler syndrome. In this study, 12 Chinese probands lacked obvious systemic phenotypes.In this study, three novel and two known mutations in the COL2A1 gene were identified in six of 16 Chinese patients with Stickler syndrome. This is the first study in a cohort of Chinese patients with Stickler syndrome, and the results expand the mutation spectrum of the COL2A1 gene. Analysis of the genotype-phenotype correlation showed that the early onset of high myopia with vitreous abnormalities may serve as a key indicator of Stickler syndrome, while the existence of mandibular protrusion in pediatric patients may be an efficient indicator for the absence of mutations in COL2A1 and COL11A1.

SUBMITTER: Wang X

PROVIDER: S-EPMC4919091 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Mutation survey and genotype-phenotype analysis of COL2A1 and COL11A1 genes in 16 Chinese patients with Stickler syndrome.

Wang Xun X Jia Xiaoyun X Xiao Xueshan X Li Shiqiang S Li Jie J Li Yadi Y Wei Yantao Y Liang Xiaoling X Guo Xiangming X

Molecular vision 20160623

<h4>Purpose</h4>To identify mutations in COL2A1 and COL11A1 genes and to examine the genotype-phenotype correlation in a cohort of Chinese patients with Stickler syndrome.<h4>Methods</h4>A total of 16 Chinese probands with Stickler syndrome were recruited, including nine with a family history of an autosomal dominant pattern and seven sporadic cases. All patients underwent full ocular and systemic examinations. Sanger sequencing was used to analyze all coding and adjacent regions of the COL2A1 a ...[more]

PMID: 27390512

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Project description:PurposeOur previous study reported that 5.5% of probands with early-onset high myopia (eoHM) had mutations in COL2A1 or COL11A1. Why were the probands initially considered to have eoHM but not Stickler syndrome (STL)?MethodsProbands and family members with eoHM and mutations in COL2A1 or COL11A1 were followed up and reexamined based on the criteria for STL. Further comprehensive examinations were conducted for patients with eoHM and mutations in COL2A1 or COL11A1 and controls with eoHM without mutations in COL2A1 or COL11A1. We performed comparisons between probands, affected family members with mutations in COL2A1 or COL11A1, and controls with eoHM without mutations in COL2A1 or COL11A1.ResultsTwelve probands (8.91±4.03 years) and 14 affected family members (37.00±11.18 years) with eoHM and mutations in COL2A1 or COL11A1, as well as 30 controls with eoHM but without mutations in COL2A1 or COL11A1, were recruited. Among them, 25.0% of probands and 50.0% of affected family members met the diagnostic criteria for STL after reexamination. Posterior vitreous detachment/foveal hypoplasia (PVD/FH), hypermobility of the elbow joint (HJ), and vitreous opacity were more frequent in patients with eoHM with mutations in COL2A1 or COL11A1 than in the controls (p = 1.40 × 10-5, 3.72 × 10-4, 2.30× 10-3, respectively). HJ was more common in the probands than in the affected family members (11/12 versus 3/14; p = 3.42 × 10-4), suggesting age-dependent manifestation. EoHM presented in all the probands and in 11/14 affected family members, suggesting that it is a more common indicator of STL than the previously described vitreoretinal abnormalities, especially in children. The rate of STL diagnosis could increase from 25.0% to 66.7% for probands and from 50.0% to 92.9% for affected family members if eoHM, PVD/FH, and HJ are added to the diagnostic criteria.ConclusionsIn summary, it is not easy to differentiate STL from eoHM with routine ocular examination in outpatient clinics. Awareness of atypical phenotypes and newly recognized signs may be of help in identifying atypical STL, especially in children at eye clinics.

Dataset Information

Mutation survey and genotype-phenotype analysis of COL2A1 and COL11A1 genes in 16 Chinese patients with Stickler syndrome.

Publications

Mutation survey and genotype-phenotype analysis of COL2A1 and COL11A1 genes in 16 Chinese patients with Stickler syndrome.

Similar Datasets

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