Cargando…

A novel splice donor site mutation in EPHA2 caused congenital cataract in a Chinese family

BACKGROUND: Congenital cataract is a rare disorder characterized by crystallin denaturation, which becomes a major cause of childhood blindness. Although more than fifty pathogenic genes for congenital cataract have been reported, the genetic causes of many cataract patients remain unknown. In this...

Descripción completa

Detalles Bibliográficos
Autores principales: Bu, Juan, He, Sijie, Wang, Lejin, Li, Jiankang, Liu, Jing, Zhang, Xiuqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966373/
https://www.ncbi.nlm.nih.gov/pubmed/27380975
http://dx.doi.org/10.4103/0301-4738.185597
_version_ 1782445368941740032
author Bu, Juan
He, Sijie
Wang, Lejin
Li, Jiankang
Liu, Jing
Zhang, Xiuqing
author_facet Bu, Juan
He, Sijie
Wang, Lejin
Li, Jiankang
Liu, Jing
Zhang, Xiuqing
author_sort Bu, Juan
collection PubMed
description BACKGROUND: Congenital cataract is a rare disorder characterized by crystallin denaturation, which becomes a major cause of childhood blindness. Although more than fifty pathogenic genes for congenital cataract have been reported, the genetic causes of many cataract patients remain unknown. In this study, the aim is to identify the genetic cause of a five-generation Chinese autosomal dominant congenital cataract family. METHODS: Whole exome sequencing (WES) was performed on three affected and one unaffected member of the family, known causative genes were scanned first. Sanger sequencing was used to validate co-segregation of the candidate variant in the family. The impact on the transcript and amino acid sequences of the variant was further analyzed. RESULTS: We identified a novel splice donor site mutation c. 2825+1G >A in EPHA2 that was absent in public and in-house databases and showed co-segregation in the family. This variant resulted in an altered splice that led to protein truncation. CONCLUSIONS: The mutation we identified was responsible for congenital cataract in our studied family. Our findings broaden the spectrum of causative mutations in EPHA2 gene for congenital cataract and suggest that WES is an efficient strategy to scan variants in known causative genes for genetically heterogeneous diseases.
format Online
Article
Text
id pubmed-4966373
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Medknow Publications & Media Pvt Ltd
record_format MEDLINE/PubMed
spelling pubmed-49663732016-08-10 A novel splice donor site mutation in EPHA2 caused congenital cataract in a Chinese family Bu, Juan He, Sijie Wang, Lejin Li, Jiankang Liu, Jing Zhang, Xiuqing Indian J Ophthalmol Original Article BACKGROUND: Congenital cataract is a rare disorder characterized by crystallin denaturation, which becomes a major cause of childhood blindness. Although more than fifty pathogenic genes for congenital cataract have been reported, the genetic causes of many cataract patients remain unknown. In this study, the aim is to identify the genetic cause of a five-generation Chinese autosomal dominant congenital cataract family. METHODS: Whole exome sequencing (WES) was performed on three affected and one unaffected member of the family, known causative genes were scanned first. Sanger sequencing was used to validate co-segregation of the candidate variant in the family. The impact on the transcript and amino acid sequences of the variant was further analyzed. RESULTS: We identified a novel splice donor site mutation c. 2825+1G >A in EPHA2 that was absent in public and in-house databases and showed co-segregation in the family. This variant resulted in an altered splice that led to protein truncation. CONCLUSIONS: The mutation we identified was responsible for congenital cataract in our studied family. Our findings broaden the spectrum of causative mutations in EPHA2 gene for congenital cataract and suggest that WES is an efficient strategy to scan variants in known causative genes for genetically heterogeneous diseases. Medknow Publications & Media Pvt Ltd 2016-05 /pmc/articles/PMC4966373/ /pubmed/27380975 http://dx.doi.org/10.4103/0301-4738.185597 Text en Copyright: © Indian Journal of Ophthalmology http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
spellingShingle Original Article
Bu, Juan
He, Sijie
Wang, Lejin
Li, Jiankang
Liu, Jing
Zhang, Xiuqing
A novel splice donor site mutation in EPHA2 caused congenital cataract in a Chinese family
title A novel splice donor site mutation in EPHA2 caused congenital cataract in a Chinese family
title_full A novel splice donor site mutation in EPHA2 caused congenital cataract in a Chinese family
title_fullStr A novel splice donor site mutation in EPHA2 caused congenital cataract in a Chinese family
title_full_unstemmed A novel splice donor site mutation in EPHA2 caused congenital cataract in a Chinese family
title_short A novel splice donor site mutation in EPHA2 caused congenital cataract in a Chinese family
title_sort novel splice donor site mutation in epha2 caused congenital cataract in a chinese family
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966373/
https://www.ncbi.nlm.nih.gov/pubmed/27380975
http://dx.doi.org/10.4103/0301-4738.185597
work_keys_str_mv AT bujuan anovelsplicedonorsitemutationinepha2causedcongenitalcataractinachinesefamily
AT hesijie anovelsplicedonorsitemutationinepha2causedcongenitalcataractinachinesefamily
AT wanglejin anovelsplicedonorsitemutationinepha2causedcongenitalcataractinachinesefamily
AT lijiankang anovelsplicedonorsitemutationinepha2causedcongenitalcataractinachinesefamily
AT liujing anovelsplicedonorsitemutationinepha2causedcongenitalcataractinachinesefamily
AT zhangxiuqing anovelsplicedonorsitemutationinepha2causedcongenitalcataractinachinesefamily
AT bujuan novelsplicedonorsitemutationinepha2causedcongenitalcataractinachinesefamily
AT hesijie novelsplicedonorsitemutationinepha2causedcongenitalcataractinachinesefamily
AT wanglejin novelsplicedonorsitemutationinepha2causedcongenitalcataractinachinesefamily
AT lijiankang novelsplicedonorsitemutationinepha2causedcongenitalcataractinachinesefamily
AT liujing novelsplicedonorsitemutationinepha2causedcongenitalcataractinachinesefamily
AT zhangxiuqing novelsplicedonorsitemutationinepha2causedcongenitalcataractinachinesefamily