Cargando…

A Large Novel Deletion Downstream of PAX6 Gene in a Chinese Family with Ocular Coloboma

PURPOSE: The paired box gene 6 (PAX6) is an essential transcription factor for eye formation. Genetic alterations in PAX6 can lead to various ocular malformations including aniridia. The purpose of this study was to identify genetic defects as the underlying cause of familial ocular coloboma in a la...

Descripción completa

Detalles Bibliográficos
Autores principales: Guo, Hong, Dai, Limeng, Huang, Yanming, Liao, Qiong, Bai, Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859656/
https://www.ncbi.nlm.nih.gov/pubmed/24349436
http://dx.doi.org/10.1371/journal.pone.0083073
_version_ 1782295449155141632
author Guo, Hong
Dai, Limeng
Huang, Yanming
Liao, Qiong
Bai, Yun
author_facet Guo, Hong
Dai, Limeng
Huang, Yanming
Liao, Qiong
Bai, Yun
author_sort Guo, Hong
collection PubMed
description PURPOSE: The paired box gene 6 (PAX6) is an essential transcription factor for eye formation. Genetic alterations in PAX6 can lead to various ocular malformations including aniridia. The purpose of this study was to identify genetic defects as the underlying cause of familial ocular coloboma in a large Chinese family. METHODS: After linkage analysis was carried out in this family, all exons of PAX6 in the proband were sequenced by the Sanger sequencing technique. Then the genome of the proband was evaluated by a microarray-based comparative genomic hybridization (aCGH). Quantitative real-time PCR was applied to verify the abnormal aCGH findings. RESULTS: All patients presented bilateral partial coloboma of iris, severe congenital nystagmus, hyperpresbyopia and congenital posterior polar cataracts. Two-point linkage analysis in the autosomal dominant family showed loss of heterozygosity at the D11S914 locus. There was no pathogenic mutation in the exons of PAX6. The aCGH analysis revealed a 681 kb heterozygous deletion on chromosome 11p13. Quantitative real-time PCR verified the deletion in the patients and further confirmed this deletion cosegregation with the ocular coloboma phenotype in the family. CONCLUSIONS: The 681 kb large deletion of chromosome 11p13 downstream of PAX6 is the genetic cause of the familial ocular coloboma in this large Chinese family. aCGH should be applied if there is a negative result for the mutation detection of PAX6 in patients with ocular coloboma.
format Online
Article
Text
id pubmed-3859656
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-38596562013-12-13 A Large Novel Deletion Downstream of PAX6 Gene in a Chinese Family with Ocular Coloboma Guo, Hong Dai, Limeng Huang, Yanming Liao, Qiong Bai, Yun PLoS One Research Article PURPOSE: The paired box gene 6 (PAX6) is an essential transcription factor for eye formation. Genetic alterations in PAX6 can lead to various ocular malformations including aniridia. The purpose of this study was to identify genetic defects as the underlying cause of familial ocular coloboma in a large Chinese family. METHODS: After linkage analysis was carried out in this family, all exons of PAX6 in the proband were sequenced by the Sanger sequencing technique. Then the genome of the proband was evaluated by a microarray-based comparative genomic hybridization (aCGH). Quantitative real-time PCR was applied to verify the abnormal aCGH findings. RESULTS: All patients presented bilateral partial coloboma of iris, severe congenital nystagmus, hyperpresbyopia and congenital posterior polar cataracts. Two-point linkage analysis in the autosomal dominant family showed loss of heterozygosity at the D11S914 locus. There was no pathogenic mutation in the exons of PAX6. The aCGH analysis revealed a 681 kb heterozygous deletion on chromosome 11p13. Quantitative real-time PCR verified the deletion in the patients and further confirmed this deletion cosegregation with the ocular coloboma phenotype in the family. CONCLUSIONS: The 681 kb large deletion of chromosome 11p13 downstream of PAX6 is the genetic cause of the familial ocular coloboma in this large Chinese family. aCGH should be applied if there is a negative result for the mutation detection of PAX6 in patients with ocular coloboma. Public Library of Science 2013-12-11 /pmc/articles/PMC3859656/ /pubmed/24349436 http://dx.doi.org/10.1371/journal.pone.0083073 Text en © 2013 Guo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Guo, Hong
Dai, Limeng
Huang, Yanming
Liao, Qiong
Bai, Yun
A Large Novel Deletion Downstream of PAX6 Gene in a Chinese Family with Ocular Coloboma
title A Large Novel Deletion Downstream of PAX6 Gene in a Chinese Family with Ocular Coloboma
title_full A Large Novel Deletion Downstream of PAX6 Gene in a Chinese Family with Ocular Coloboma
title_fullStr A Large Novel Deletion Downstream of PAX6 Gene in a Chinese Family with Ocular Coloboma
title_full_unstemmed A Large Novel Deletion Downstream of PAX6 Gene in a Chinese Family with Ocular Coloboma
title_short A Large Novel Deletion Downstream of PAX6 Gene in a Chinese Family with Ocular Coloboma
title_sort large novel deletion downstream of pax6 gene in a chinese family with ocular coloboma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859656/
https://www.ncbi.nlm.nih.gov/pubmed/24349436
http://dx.doi.org/10.1371/journal.pone.0083073
work_keys_str_mv AT guohong alargenoveldeletiondownstreamofpax6geneinachinesefamilywithocularcoloboma
AT dailimeng alargenoveldeletiondownstreamofpax6geneinachinesefamilywithocularcoloboma
AT huangyanming alargenoveldeletiondownstreamofpax6geneinachinesefamilywithocularcoloboma
AT liaoqiong alargenoveldeletiondownstreamofpax6geneinachinesefamilywithocularcoloboma
AT baiyun alargenoveldeletiondownstreamofpax6geneinachinesefamilywithocularcoloboma
AT guohong largenoveldeletiondownstreamofpax6geneinachinesefamilywithocularcoloboma
AT dailimeng largenoveldeletiondownstreamofpax6geneinachinesefamilywithocularcoloboma
AT huangyanming largenoveldeletiondownstreamofpax6geneinachinesefamilywithocularcoloboma
AT liaoqiong largenoveldeletiondownstreamofpax6geneinachinesefamilywithocularcoloboma
AT baiyun largenoveldeletiondownstreamofpax6geneinachinesefamilywithocularcoloboma