Cargando…
A Rare Novel CLCN2 Variation and Risk of Gilles de la Tourette Syndrome: Whole-Exome Sequencing in a Multiplex Family and a Follow-Up Study in a Chinese Population
Rare inherited variations in multiplex families with Gilles de la Tourette syndrome (GTS) are suggested to play an important role in the genetic etiology of GTS. In order to explore the rare inherited variations with the risk of GTS, whole-exome sequencing (WES) was performed in a family with three...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744286/ https://www.ncbi.nlm.nih.gov/pubmed/33343406 http://dx.doi.org/10.3389/fpsyt.2020.543911 |
_version_ | 1783624405490860032 |
---|---|
author | Yuan, Aihua Wang, Zengge Xu, Wen Ding, Qiang Zhao, Ying Han, Jingjing Sun, Jinhua |
author_facet | Yuan, Aihua Wang, Zengge Xu, Wen Ding, Qiang Zhao, Ying Han, Jingjing Sun, Jinhua |
author_sort | Yuan, Aihua |
collection | PubMed |
description | Rare inherited variations in multiplex families with Gilles de la Tourette syndrome (GTS) are suggested to play an important role in the genetic etiology of GTS. In order to explore the rare inherited variations with the risk of GTS, whole-exome sequencing (WES) was performed in a family with three affected patients with GTS. Among the five novel rare variations identified by WES, CLCN2 G161S was presented in three patients, but not in four unaffected individuals, and thus co-segregated with GTS. A validation study was also performed in a cohort of Chinses Han population to further examine the identified rare variants. CLCN2 G161S was genotyped in 207 sporadic patients with tic disorder including 111 patients with GTS and 489 healthy controls. Compared with that in controls [allele frequency (AF) = 0], CLCN2 G161S had higher variant AF in patients with tic (AF = 0.00483) and in patients with GTS (0.00900), respectively. However, this variant was absent from the current 1000 Genome databases, and the variant AF is very low in the current public databases including ExAC (AF = 0.00001) and gnomAD (AF = 0.00003). Our results suggest that CLCN2 G161S might play a major role in the genetic etiology of GTS, at least in a Chinese Han population. |
format | Online Article Text |
id | pubmed-7744286 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77442862020-12-18 A Rare Novel CLCN2 Variation and Risk of Gilles de la Tourette Syndrome: Whole-Exome Sequencing in a Multiplex Family and a Follow-Up Study in a Chinese Population Yuan, Aihua Wang, Zengge Xu, Wen Ding, Qiang Zhao, Ying Han, Jingjing Sun, Jinhua Front Psychiatry Psychiatry Rare inherited variations in multiplex families with Gilles de la Tourette syndrome (GTS) are suggested to play an important role in the genetic etiology of GTS. In order to explore the rare inherited variations with the risk of GTS, whole-exome sequencing (WES) was performed in a family with three affected patients with GTS. Among the five novel rare variations identified by WES, CLCN2 G161S was presented in three patients, but not in four unaffected individuals, and thus co-segregated with GTS. A validation study was also performed in a cohort of Chinses Han population to further examine the identified rare variants. CLCN2 G161S was genotyped in 207 sporadic patients with tic disorder including 111 patients with GTS and 489 healthy controls. Compared with that in controls [allele frequency (AF) = 0], CLCN2 G161S had higher variant AF in patients with tic (AF = 0.00483) and in patients with GTS (0.00900), respectively. However, this variant was absent from the current 1000 Genome databases, and the variant AF is very low in the current public databases including ExAC (AF = 0.00001) and gnomAD (AF = 0.00003). Our results suggest that CLCN2 G161S might play a major role in the genetic etiology of GTS, at least in a Chinese Han population. Frontiers Media S.A. 2020-12-03 /pmc/articles/PMC7744286/ /pubmed/33343406 http://dx.doi.org/10.3389/fpsyt.2020.543911 Text en Copyright © 2020 Yuan, Wang, Xu, Ding, Zhao, Han and Sun. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Psychiatry Yuan, Aihua Wang, Zengge Xu, Wen Ding, Qiang Zhao, Ying Han, Jingjing Sun, Jinhua A Rare Novel CLCN2 Variation and Risk of Gilles de la Tourette Syndrome: Whole-Exome Sequencing in a Multiplex Family and a Follow-Up Study in a Chinese Population |
title | A Rare Novel CLCN2 Variation and Risk of Gilles de la Tourette Syndrome: Whole-Exome Sequencing in a Multiplex Family and a Follow-Up Study in a Chinese Population |
title_full | A Rare Novel CLCN2 Variation and Risk of Gilles de la Tourette Syndrome: Whole-Exome Sequencing in a Multiplex Family and a Follow-Up Study in a Chinese Population |
title_fullStr | A Rare Novel CLCN2 Variation and Risk of Gilles de la Tourette Syndrome: Whole-Exome Sequencing in a Multiplex Family and a Follow-Up Study in a Chinese Population |
title_full_unstemmed | A Rare Novel CLCN2 Variation and Risk of Gilles de la Tourette Syndrome: Whole-Exome Sequencing in a Multiplex Family and a Follow-Up Study in a Chinese Population |
title_short | A Rare Novel CLCN2 Variation and Risk of Gilles de la Tourette Syndrome: Whole-Exome Sequencing in a Multiplex Family and a Follow-Up Study in a Chinese Population |
title_sort | rare novel clcn2 variation and risk of gilles de la tourette syndrome: whole-exome sequencing in a multiplex family and a follow-up study in a chinese population |
topic | Psychiatry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744286/ https://www.ncbi.nlm.nih.gov/pubmed/33343406 http://dx.doi.org/10.3389/fpsyt.2020.543911 |
work_keys_str_mv | AT yuanaihua ararenovelclcn2variationandriskofgillesdelatourettesyndromewholeexomesequencinginamultiplexfamilyandafollowupstudyinachinesepopulation AT wangzengge ararenovelclcn2variationandriskofgillesdelatourettesyndromewholeexomesequencinginamultiplexfamilyandafollowupstudyinachinesepopulation AT xuwen ararenovelclcn2variationandriskofgillesdelatourettesyndromewholeexomesequencinginamultiplexfamilyandafollowupstudyinachinesepopulation AT dingqiang ararenovelclcn2variationandriskofgillesdelatourettesyndromewholeexomesequencinginamultiplexfamilyandafollowupstudyinachinesepopulation AT zhaoying ararenovelclcn2variationandriskofgillesdelatourettesyndromewholeexomesequencinginamultiplexfamilyandafollowupstudyinachinesepopulation AT hanjingjing ararenovelclcn2variationandriskofgillesdelatourettesyndromewholeexomesequencinginamultiplexfamilyandafollowupstudyinachinesepopulation AT sunjinhua ararenovelclcn2variationandriskofgillesdelatourettesyndromewholeexomesequencinginamultiplexfamilyandafollowupstudyinachinesepopulation AT yuanaihua rarenovelclcn2variationandriskofgillesdelatourettesyndromewholeexomesequencinginamultiplexfamilyandafollowupstudyinachinesepopulation AT wangzengge rarenovelclcn2variationandriskofgillesdelatourettesyndromewholeexomesequencinginamultiplexfamilyandafollowupstudyinachinesepopulation AT xuwen rarenovelclcn2variationandriskofgillesdelatourettesyndromewholeexomesequencinginamultiplexfamilyandafollowupstudyinachinesepopulation AT dingqiang rarenovelclcn2variationandriskofgillesdelatourettesyndromewholeexomesequencinginamultiplexfamilyandafollowupstudyinachinesepopulation AT zhaoying rarenovelclcn2variationandriskofgillesdelatourettesyndromewholeexomesequencinginamultiplexfamilyandafollowupstudyinachinesepopulation AT hanjingjing rarenovelclcn2variationandriskofgillesdelatourettesyndromewholeexomesequencinginamultiplexfamilyandafollowupstudyinachinesepopulation AT sunjinhua rarenovelclcn2variationandriskofgillesdelatourettesyndromewholeexomesequencinginamultiplexfamilyandafollowupstudyinachinesepopulation |