Dataset Information

Targeted next-generation sequencing extends the mutational spectrums for OPA1 mutations in Chinese families with optic atrophy.

ABSTRACT: Purpose:We aim to reveal the disease-causing mutations in 15 Chinese families with optic atrophy (OA). Methods:In total, 15 families with OA were recruited in the present study. Medical histories were carefully reviewed and comprehensive ophthalmic examinations were received by all recruited patients. Targeted next-generation sequencing (NGS) was selectively performed on all probands for mutation detection. Intrafamilial cosegregation and in-silico analyses were subsequently applied to predict the potential pathogenic effects of identified mutations. Results:All included patients presented bilateral vision loss. Their fundus photographs showed temporal or total pallor of the optic discs. Fourteen mutations in the optic atrophy 1 (OPA1) gene were revealed as disease-causing mutations for the 15 families, including eight novel (c.968A>G, c.193C>G, c.1071dupT, c.987_988del, c.2012+2T>G, c.1036-1G>C, c.2126A>G, and c.1036_1038del) and six recurrent (c.1499G>A, c.1800C>A, c.1034G>A, c.2873_2876del, c.112C>T, and c.804_805del) mutations. Conclusions:In conclusion, our study expands the mutational spectrum for the OPA1 gene and implies targeted NGS as an effective approach for the genetic diagnosis of OA, which might help to improve the clinical diagnosis for patients with OA.

SUBMITTER: Wang Y

PROVIDER: S-EPMC6982427 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Targeted next-generation sequencing extends the mutational spectrums for <i>OPA1</i> mutations in Chinese families with optic atrophy.

Wang Yuwei Y Xu Min M Liu Xiaoxing X Huang Yongheng Y Zhou Yao Y Liu Qinghuai Q Chen Xue X Zhao Chen C Wang Min M

Molecular vision 20191231

<h4>Purpose</h4>We aim to reveal the disease-causing mutations in 15 Chinese families with optic atrophy (OA).<h4>Methods</h4>In total, 15 families with OA were recruited in the present study. Medical histories were carefully reviewed and comprehensive ophthalmic examinations were received by all recruited patients. Targeted next-generation sequencing (NGS) was selectively performed on all probands for mutation detection. Intrafamilial cosegregation and in-silico analyses were subsequently appli ...[more]

PMID: 32025183

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Project description:We aim to determine genetic lesions with a phenotypic correlation in four Chinese families with autosomal recessive retinitis pigmentosa (RP).Medical histories were carefully reviewed. All patients received comprehensive ophthalmic evaluations. The next-generation sequencing (NGS) approach targeting a panel of 205 retinal disease-relevant genes and 15 candidate genes was selectively performed on probands from the four recruited families for mutation detection. Online predictive software and crystal structure modeling were also applied to test the potential pathogenic effects of identified mutations.Of the four families, two were diagnosed with RP sino pigmento (RPSP). Patients with RPSP claimed to have earlier RP age of onset but slower disease progression. Five mutations in the eyes shut homolog (EYS) gene, involving two novel (c.7228+1G>A and c.9248G>A) and three recurrent mutations (c.4957dupA, c.6416G>A and c.6557G>A), were found as RP causative in the four families. The missense variant c.5093T>C was determined to be a variant of unknown significance (VUS) due to the variant's colocalization in the same allele with the reported pathogenic mutation c.6416G>A. The two novel variants were further confirmed absent in 100 unrelated healthy controls. Online predictive software indicated potential pathogenicity of the three missense mutations. Further, crystal structural modeling suggested generation of two abnormal hydrogen bonds by the missense mutation p.G2186E (c.6557G>A) and elongation of its neighboring ?-sheet induced by p.G3083D (c.9248G>A), which could alter the tertiary structure of the eys protein and thus interrupt its physicochemical properties.Taken together, with the targeted NGS approach, we reveal novel EYS mutations and prove the efficiency of targeted NGS in the genetic diagnoses of RP. We also first report the correlation between EYS mutations and RPSP. The genotypic-phenotypic relationship in all Chinese patients carrying mutations in the EYS gene were also reviewed and summarized.

Dataset Information

Targeted next-generation sequencing extends the mutational spectrums for OPA1 mutations in Chinese families with optic atrophy.

Publications

Targeted next-generation sequencing extends the mutational spectrums for <i>OPA1</i> mutations in Chinese families with optic atrophy.

Similar Datasets

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