Identification of candidate genes for congenital heart defects on proximal chromosome 8p

With the application of advanced molecular cytogenetic techniques, the number of patients identified as having abnormal chromosome 8p has increased progressively. Individuals with terminal 8p deletion have been extensively described in previous studies. The manifestations usually include cardiac ano...

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Main Authors:	Li, Tingting, Liu, Chunjie, Xu, Yuejuan, Guo, Qianqian, Chen, Sun, Sun, Kun, Xu, Rang
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5093561/

id	pubmed-5093561
recordtype	oai_dc
spelling	pubmed-50935612016-11-10 Identification of candidate genes for congenital heart defects on proximal chromosome 8p Li, Tingting Liu, Chunjie Xu, Yuejuan Guo, Qianqian Chen, Sun Sun, Kun Xu, Rang Article With the application of advanced molecular cytogenetic techniques, the number of patients identified as having abnormal chromosome 8p has increased progressively. Individuals with terminal 8p deletion have been extensively described in previous studies. The manifestations usually include cardiac anomalies, developmental delay/mental retardation, craniofacial abnormalities, and multiple other minor anomalies. However, some patients with proximal deletion also presented with similar phenotypic features. Here we describe a female child with an 18.5-Mb deletion at 8p11.23–p22 that include the cardiac-associated loci NKX2-6 and NRG1. Further mutation screening of these two candidate genes in 143 atrial septal defect patients, two heterozygous mutations NKX2-6 (c.1A > T) and NRG1 (c.1652G > A) were identified. The mutations were described for the first time in patients with congenital heart disease (CHD). The c.1A > T NKX2-6 generated a protein truncated by 45 amino acids with a decreased level of mRNA expression, whereas the NRG1 mutation had no significant effect on protein functions. Our findings suggest that 8p21-8p12 may be another critical region for 8p-associated CHD, and some cardiac malformations might be due to NKX2-6 haploinsufficiency. This study also links the NKX2-6 mutation to ASD for the first time, providing novel insight into the molecular underpinning of this common form of CHD. Nature Publishing Group 2016-11-03 /pmc/articles/PMC5093561/ /pubmed/27808268 http://dx.doi.org/10.1038/srep36133 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Li, Tingting Liu, Chunjie Xu, Yuejuan Guo, Qianqian Chen, Sun Sun, Kun Xu, Rang
spellingShingle	Li, Tingting Liu, Chunjie Xu, Yuejuan Guo, Qianqian Chen, Sun Sun, Kun Xu, Rang Identification of candidate genes for congenital heart defects on proximal chromosome 8p
author_facet	Li, Tingting Liu, Chunjie Xu, Yuejuan Guo, Qianqian Chen, Sun Sun, Kun Xu, Rang
author_sort	Li, Tingting
title	Identification of candidate genes for congenital heart defects on proximal chromosome 8p
title_short	Identification of candidate genes for congenital heart defects on proximal chromosome 8p
title_full	Identification of candidate genes for congenital heart defects on proximal chromosome 8p
title_fullStr	Identification of candidate genes for congenital heart defects on proximal chromosome 8p
title_full_unstemmed	Identification of candidate genes for congenital heart defects on proximal chromosome 8p
title_sort	identification of candidate genes for congenital heart defects on proximal chromosome 8p
description	With the application of advanced molecular cytogenetic techniques, the number of patients identified as having abnormal chromosome 8p has increased progressively. Individuals with terminal 8p deletion have been extensively described in previous studies. The manifestations usually include cardiac anomalies, developmental delay/mental retardation, craniofacial abnormalities, and multiple other minor anomalies. However, some patients with proximal deletion also presented with similar phenotypic features. Here we describe a female child with an 18.5-Mb deletion at 8p11.23–p22 that include the cardiac-associated loci NKX2-6 and NRG1. Further mutation screening of these two candidate genes in 143 atrial septal defect patients, two heterozygous mutations NKX2-6 (c.1A > T) and NRG1 (c.1652G > A) were identified. The mutations were described for the first time in patients with congenital heart disease (CHD). The c.1A > T NKX2-6 generated a protein truncated by 45 amino acids with a decreased level of mRNA expression, whereas the NRG1 mutation had no significant effect on protein functions. Our findings suggest that 8p21-8p12 may be another critical region for 8p-associated CHD, and some cardiac malformations might be due to NKX2-6 haploinsufficiency. This study also links the NKX2-6 mutation to ASD for the first time, providing novel insight into the molecular underpinning of this common form of CHD.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5093561/
_version_	1613711028643692544

Identification of candidate genes for congenital heart defects on proximal chromosome 8p

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