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01.12.2018 | Research article | Ausgabe 1/2018 Open Access

BMC Medical Genetics 1/2018

Novel mutations in HSF4 cause congenital cataracts in Chinese families

Zeitschrift:
BMC Medical Genetics > Ausgabe 1/2018
Autoren:
Zongfu Cao, Yihua Zhu, Lijuan Liu, Shuangqing Wu, Bing Liu, Jianfu Zhuang, Yi Tong, Xiaole Chen, Yongqing Xie, Kaimei Nie, Cailing Lu, Xu Ma, Juhua Yang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12881-018-0636-3) contains supplementary material, which is available to authorized users.
Zongfu Cao, Yihua Zhu and Lijuan Liu contributed equally to this work.

Abstract

Background

Congenital cataract, a kind of cataract presenting at birth or during early childhood, is a leading cause of childhood blindness. To date, more than 30 genes on different chromosomes are known to cause this disorder. This study aimed to identify the HSF4 mutations in a cohort from Chinese families affected with congenital cataracts.

Methods

Forty-two unrelated non-syndromic congenital cataract families and 112 ethnically matched controls from southeast China were recruited from the southeast of China. We employed Sanger sequencing method to discover the variants. To confirm the novel mutations, STR haplotypes were constructed to check the co-segregation with congenital cataract. The pathogenic potential of the novel mutations were assessed using bioinformatics tools including SIFT, Polyphen2, and Human Splicing Finder. The pathogenicity of all the mutations was evaluated by the guidelines of American College of Medical Genetics and InterVar software.

Results

No previously reported HSF4 mutations were found in all the congenital cataract families. Five novel HSF4 mutations including c.187 T > C (p.Phe63Leu), c.218G > T (p.Arg73Leu), c.233A > G (p.Tyr78Cys), IVS5 c.233-1G > A and c.314G > C (p.Ser105Thr) were identified in five unrelated families with congenital cataracts, respectively. These mutations co-segregated with all affected individuals in each family were not observed in the unaffected family members or in 112 unrelated controls. All five mutations were categorized to be the disease “pathogenic” according to ACMG guidelines and using InterVar software. Mutations in the HSF4 were responsible for 11.90% Chinese families with congenital cataracts in our cohort.

Conclusions

In the study, we identified five novel HSF4 mutations in Chinese families with congenital cataracts. Our results expand the spectrum of HSF4 mutations causing congenital cataracts, which may be helpful for the molecular diagnosis of congenital cataracts in the era of precision medicine.
Zusatzmaterial
Additional file 1: Table S1. The PCR primers and conditions for all the tested genes. The selected hot spot exons and splice junctions of these genes were amplified by PCR from genomic DNA using the primers and conditions. (DOCX 29 kb)
12881_2018_636_MOESM1_ESM.docx
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