Cargando…

A novel, homozygous nonsense variant of the CDHR1 gene in a Chinese family causes autosomal recessive retinal dystrophy by NGS‐based genetic diagnosis

Retinal dystrophy is an inherited, heterogeneous, chronic and progressive disorder of visual functions. The mutations of patients with autosomal recessive retinal retinopathy cone‐and‐rod dysfunction and macular dystrophy have not been well described in the Chinese population. In this study, a three...

Descripción completa

Detalles Bibliográficos
Autores principales: Fu, Jiewen, Ma, Lu, Cheng, Jingliang, Yang, Lisha, Wei, Chunli, Fu, Shangyi, Lv, Hongbin, Chen, Rui, Fu, Junjiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201214/
https://www.ncbi.nlm.nih.gov/pubmed/30160356
http://dx.doi.org/10.1111/jcmm.13841
_version_ 1783365465434750976
author Fu, Jiewen
Ma, Lu
Cheng, Jingliang
Yang, Lisha
Wei, Chunli
Fu, Shangyi
Lv, Hongbin
Chen, Rui
Fu, Junjiang
author_facet Fu, Jiewen
Ma, Lu
Cheng, Jingliang
Yang, Lisha
Wei, Chunli
Fu, Shangyi
Lv, Hongbin
Chen, Rui
Fu, Junjiang
author_sort Fu, Jiewen
collection PubMed
description Retinal dystrophy is an inherited, heterogeneous, chronic and progressive disorder of visual functions. The mutations of patients with autosomal recessive retinal retinopathy cone‐and‐rod dysfunction and macular dystrophy have not been well described in the Chinese population. In this study, a three‐generation Chinese retinal dystrophy family was recruited. Ophthalmic examinations were performed. Targeted next generation sequencing (TGS) was used to identify causative genes, and Sanger sequencing was conducted to verify candidate mutations and co‐segregation. Reverse transcription (RT)‐PCR was applied to investigate the spatial and temporal expression patterns of cdhr1 gene in mouse. A novel, homozygous, deleterious and nonsense variant (c.T1641A; p.Y547*) in the CDHR1 gene was identified in the family with autosomal recessive retinal dystrophy, which was co‐segregated with the clinical phenotypes in this family. RT‐PCR analysis revealed that cdhr1 is ubiquitously expressed in eye, particularly very high expression in retina; high expression in lens, sclera, and cornea; and high expression in brain. In conclusion, our study is the first to indicate that the novel homozygous variant c.T1641A (p.Y547*) in the CHDR1 gene might be the disease‐causing mutation for retinal dystrophy in our patient, extending its mutation spectrums. These findings further the understanding of the molecular pathogenesis of this disease and provide new insights for diagnosis as well as new implications for genetic counselling.
format Online
Article
Text
id pubmed-6201214
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-62012142018-11-01 A novel, homozygous nonsense variant of the CDHR1 gene in a Chinese family causes autosomal recessive retinal dystrophy by NGS‐based genetic diagnosis Fu, Jiewen Ma, Lu Cheng, Jingliang Yang, Lisha Wei, Chunli Fu, Shangyi Lv, Hongbin Chen, Rui Fu, Junjiang J Cell Mol Med Original Articles Retinal dystrophy is an inherited, heterogeneous, chronic and progressive disorder of visual functions. The mutations of patients with autosomal recessive retinal retinopathy cone‐and‐rod dysfunction and macular dystrophy have not been well described in the Chinese population. In this study, a three‐generation Chinese retinal dystrophy family was recruited. Ophthalmic examinations were performed. Targeted next generation sequencing (TGS) was used to identify causative genes, and Sanger sequencing was conducted to verify candidate mutations and co‐segregation. Reverse transcription (RT)‐PCR was applied to investigate the spatial and temporal expression patterns of cdhr1 gene in mouse. A novel, homozygous, deleterious and nonsense variant (c.T1641A; p.Y547*) in the CDHR1 gene was identified in the family with autosomal recessive retinal dystrophy, which was co‐segregated with the clinical phenotypes in this family. RT‐PCR analysis revealed that cdhr1 is ubiquitously expressed in eye, particularly very high expression in retina; high expression in lens, sclera, and cornea; and high expression in brain. In conclusion, our study is the first to indicate that the novel homozygous variant c.T1641A (p.Y547*) in the CHDR1 gene might be the disease‐causing mutation for retinal dystrophy in our patient, extending its mutation spectrums. These findings further the understanding of the molecular pathogenesis of this disease and provide new insights for diagnosis as well as new implications for genetic counselling. John Wiley and Sons Inc. 2018-08-30 2018-11 /pmc/articles/PMC6201214/ /pubmed/30160356 http://dx.doi.org/10.1111/jcmm.13841 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Fu, Jiewen
Ma, Lu
Cheng, Jingliang
Yang, Lisha
Wei, Chunli
Fu, Shangyi
Lv, Hongbin
Chen, Rui
Fu, Junjiang
A novel, homozygous nonsense variant of the CDHR1 gene in a Chinese family causes autosomal recessive retinal dystrophy by NGS‐based genetic diagnosis
title A novel, homozygous nonsense variant of the CDHR1 gene in a Chinese family causes autosomal recessive retinal dystrophy by NGS‐based genetic diagnosis
title_full A novel, homozygous nonsense variant of the CDHR1 gene in a Chinese family causes autosomal recessive retinal dystrophy by NGS‐based genetic diagnosis
title_fullStr A novel, homozygous nonsense variant of the CDHR1 gene in a Chinese family causes autosomal recessive retinal dystrophy by NGS‐based genetic diagnosis
title_full_unstemmed A novel, homozygous nonsense variant of the CDHR1 gene in a Chinese family causes autosomal recessive retinal dystrophy by NGS‐based genetic diagnosis
title_short A novel, homozygous nonsense variant of the CDHR1 gene in a Chinese family causes autosomal recessive retinal dystrophy by NGS‐based genetic diagnosis
title_sort novel, homozygous nonsense variant of the cdhr1 gene in a chinese family causes autosomal recessive retinal dystrophy by ngs‐based genetic diagnosis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201214/
https://www.ncbi.nlm.nih.gov/pubmed/30160356
http://dx.doi.org/10.1111/jcmm.13841
work_keys_str_mv AT fujiewen anovelhomozygousnonsensevariantofthecdhr1geneinachinesefamilycausesautosomalrecessiveretinaldystrophybyngsbasedgeneticdiagnosis
AT malu anovelhomozygousnonsensevariantofthecdhr1geneinachinesefamilycausesautosomalrecessiveretinaldystrophybyngsbasedgeneticdiagnosis
AT chengjingliang anovelhomozygousnonsensevariantofthecdhr1geneinachinesefamilycausesautosomalrecessiveretinaldystrophybyngsbasedgeneticdiagnosis
AT yanglisha anovelhomozygousnonsensevariantofthecdhr1geneinachinesefamilycausesautosomalrecessiveretinaldystrophybyngsbasedgeneticdiagnosis
AT weichunli anovelhomozygousnonsensevariantofthecdhr1geneinachinesefamilycausesautosomalrecessiveretinaldystrophybyngsbasedgeneticdiagnosis
AT fushangyi anovelhomozygousnonsensevariantofthecdhr1geneinachinesefamilycausesautosomalrecessiveretinaldystrophybyngsbasedgeneticdiagnosis
AT lvhongbin anovelhomozygousnonsensevariantofthecdhr1geneinachinesefamilycausesautosomalrecessiveretinaldystrophybyngsbasedgeneticdiagnosis
AT chenrui anovelhomozygousnonsensevariantofthecdhr1geneinachinesefamilycausesautosomalrecessiveretinaldystrophybyngsbasedgeneticdiagnosis
AT fujunjiang anovelhomozygousnonsensevariantofthecdhr1geneinachinesefamilycausesautosomalrecessiveretinaldystrophybyngsbasedgeneticdiagnosis
AT fujiewen novelhomozygousnonsensevariantofthecdhr1geneinachinesefamilycausesautosomalrecessiveretinaldystrophybyngsbasedgeneticdiagnosis
AT malu novelhomozygousnonsensevariantofthecdhr1geneinachinesefamilycausesautosomalrecessiveretinaldystrophybyngsbasedgeneticdiagnosis
AT chengjingliang novelhomozygousnonsensevariantofthecdhr1geneinachinesefamilycausesautosomalrecessiveretinaldystrophybyngsbasedgeneticdiagnosis
AT yanglisha novelhomozygousnonsensevariantofthecdhr1geneinachinesefamilycausesautosomalrecessiveretinaldystrophybyngsbasedgeneticdiagnosis
AT weichunli novelhomozygousnonsensevariantofthecdhr1geneinachinesefamilycausesautosomalrecessiveretinaldystrophybyngsbasedgeneticdiagnosis
AT fushangyi novelhomozygousnonsensevariantofthecdhr1geneinachinesefamilycausesautosomalrecessiveretinaldystrophybyngsbasedgeneticdiagnosis
AT lvhongbin novelhomozygousnonsensevariantofthecdhr1geneinachinesefamilycausesautosomalrecessiveretinaldystrophybyngsbasedgeneticdiagnosis
AT chenrui novelhomozygousnonsensevariantofthecdhr1geneinachinesefamilycausesautosomalrecessiveretinaldystrophybyngsbasedgeneticdiagnosis
AT fujunjiang novelhomozygousnonsensevariantofthecdhr1geneinachinesefamilycausesautosomalrecessiveretinaldystrophybyngsbasedgeneticdiagnosis