Dataset Information

Mutation spectrum of PAX6 and clinical findings in 95 Chinese patients with aniridia.

ABSTRACT: Purpose:Aniridia is a rare congenital panocular disease caused by mutations in PAX6. The purposes of this study were to clarify the mutation features of PAX6 in a cohort of Chinese patients with aniridia and to describe their clinical characteristics. Methods:We recruited 95 patients from 65 unrelated families clinically diagnosed with aniridia. All patients underwent ophthalmic examinations. Sanger sequencing and multiplex ligation probe amplification of PAX6 were performed to detect intragenic variants and copy number variations (CNVs). Results:We identified 58 disease-causing mutations in PAX6 in 63 families; the detection rate was 96.9%. The 58 mutations included frameshift indels (27.6%), splice site changes (25.9%), nonsense mutations (20.7%), CNVs (19.0%), missense mutations (3.4%), run-on mutations (1.7%), and a synonymous mutation (1.7%). Clinical examinations revealed that 71 patients had complete or almost complete iris loss, 16 patients showed partial iris loss, and six patients had a full iris but with an abnormal structure. Conclusions:The results confirmed that mutations in PAX6 are the predominant cause of aniridia, and the majority are loss-of-function mutations that usually result in classical aniridia. In contrast, missense mutations, run-on mutations, and small numbers of splicing mutations mostly lead to atypical aniridia and an intrafamilial phenotypic variability of iris hypoplasia.

SUBMITTER: You B

PROVIDER: S-EPMC7093334 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Mutation spectrum of <i>PAX6</i> and clinical findings in 95 Chinese patients with aniridia.

You Bing B Zhang Xiaohui X Xu Ke K Xie Yue Y Ye Hanwen H Li Yang Y

Molecular vision 20200326

<h4>Purpose</h4>Aniridia is a rare congenital panocular disease caused by mutations in <i>PAX6</i>. The purposes of this study were to clarify the mutation features of <i>PAX6</i> in a cohort of Chinese patients with aniridia and to describe their clinical characteristics.<h4>Methods</h4>We recruited 95 patients from 65 unrelated families clinically diagnosed with aniridia. All patients underwent ophthalmic examinations. Sanger sequencing and multiplex ligation probe amplification of <i>PAX6</i> ...[more]

PMID: 32214788

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Project description:BACKGROUND:Congenital aniridia is a severe autosomal dominant binocular developmental disorder, the primary feature of which is congenital absence or hypoplasia of the iris. PAX6 is the main disease-causing gene of congenital aniridia; inheritance is autosomal dominant. But the current mutations do not fully explain this disorder. METHODS:We investigated the mutation profile of genes related in three Chinese families with congenital aniridia through targeted sequencing technology. And we validated the candidate variants by PCR-based Sanger sequencing. Different degree impairments of islet function were observed in the patients with aniridia by carbohydrate tolerance butter and insulin release tests in our study. RESULTS:We identified four novel mutations of PAX6 from three Chinese families with congenital aniridia, which included heterozygous double mutation c.879_880delCA (p.S294Cfs*46) and c.1124C>G (p.P375R) in Family 1 with three patients, heterozygous frameshift mutation c.308delG (p.P103Qfs*21) in Family 2 with one patient, and c.1192delT (p.S398Pfs*126) in Family 3 with two patients. The three frameshift mutations of PAX6 are co-segregated with the aniridia from controls in the families, but the novel missense mutation is not co-segregated with the phenotype. The frameshift mutations in Family 1 and Family 2 have effects to truncate the protein, but the frameshift mutation in Family 3 will prolong it. We confirmed the phenomenon of male gonadal mosaicism of PAX6 by the sequencing of two linked novel mutations in Family 1. Most of the patients with isolated aniridia have different degrees of islet damage through related clinical tests. CONCLUSION:It is therefore noteworthy that we found different types of pathogenic mutation, which have effects of truncating or prolonging protein leaded by frameshift mutation. Our results of this study extended the pathogenic mutation spectrum of PAX6 for congenital aniridia and demonstrated the male germline chimerism by molecular experiments.

Dataset Information

Mutation spectrum of PAX6 and clinical findings in 95 Chinese patients with aniridia.

Publications

Mutation spectrum of <i>PAX6</i> and clinical findings in 95 Chinese patients with aniridia.

Similar Datasets

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