Mutation screening of the SLC26A4 gene in a cohort of 192 Chinese patients with congenital hypothyroidism
ABSTRACT Objective Pendred syndrome (PS) is an autosomal recessive disorder characterised by sensorineural hearing loss and thyroid dyshormonogenesis. It is caused by biallelic mutations in the SLC26A4 gene encoding for pendrin. Hypothyroidism in PS can be present from birth and therefore diagnose...
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2016-02-01
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doaj-de02f195c2fc4e09a91431aceea5d9e52020-11-25T01:31:21ZengBrazilian Society of Endocrinology and MetabolismArchives of Endocrinology and Metabolism2359-42922016-02-0160432332710.1590/2359-3997000000108S2359-39972016000400323Mutation screening of the SLC26A4 gene in a cohort of 192 Chinese patients with congenital hypothyroidismChunyun FuHaiyang ZhengShujie ZhangYun ChenJiasun SuJin WangBobo XieXuyun HuXin FanJingsi LuoChuan LiRongyu ChenYiping ShenShaoke ChenABSTRACT Objective Pendred syndrome (PS) is an autosomal recessive disorder characterised by sensorineural hearing loss and thyroid dyshormonogenesis. It is caused by biallelic mutations in the SLC26A4 gene encoding for pendrin. Hypothyroidism in PS can be present from birth and therefore diagnosed by neonatal screening. The aim of this study was to examine the SLC26A4 mutation spectrum and prevalence among congenital hypothyroidism (CH) patients in the Guangxi Zhuang Autonomous Region of China and to establish how frequently PS causes hearing impairment in our patients with CH. Subjects and methods Blood samples were collected from 192 CH patients in Guangxi Zhuang Autonomous Region, China, and genomic DNA was extracted from peripheral blood leukocytes. All exons of the SLC26A4 gene together with their exon-intron boundaries were screened by next-generation sequencing. Patients with SLC26A4 mutations underwent a complete audiological evaluation including otoscopic examination, audiometry and morphological evaluation of the inner ear. Results Next generation sequencing analysis of SLC26A4 in 192 CH patients revealed five different heterozygous variations in eight individuals (8/192, 4%). The prevalence of SLC26A4 mutations was 4% among studied Chinese CH. Three of the eight were diagnosed as enlargement of the vestibular aqueduct (EVA), no PS were found in our 192 CH patients. The mutations included one novel missense variant p.P469S, as well as four known missense variants, namely p.V233L, p.M147I, p.V609G and p.D661E. Of the eight patients identified with SLC26A4 variations in our study, seven patients showed normal size/location of thyroid gland, and one patients showed a decreased size one. Conclusions The prevalence of SLC26A4 pathogenic variants was 4% among studied Chinese patients with CH. Our study expanded the SLC26A4 mutation spectrum, provided the best estimation of SLC26A4 mutation rate for Chinese CH patients and indicated the rarity of PS as a cause of CH.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972016000400323&lng=en&tlng=enCongenital hypothyroidismPendred syndromeSLC26A4gene mutationsChina |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chunyun Fu Haiyang Zheng Shujie Zhang Yun Chen Jiasun Su Jin Wang Bobo Xie Xuyun Hu Xin Fan Jingsi Luo Chuan Li Rongyu Chen Yiping Shen Shaoke Chen |
spellingShingle |
Chunyun Fu Haiyang Zheng Shujie Zhang Yun Chen Jiasun Su Jin Wang Bobo Xie Xuyun Hu Xin Fan Jingsi Luo Chuan Li Rongyu Chen Yiping Shen Shaoke Chen Mutation screening of the SLC26A4 gene in a cohort of 192 Chinese patients with congenital hypothyroidism Archives of Endocrinology and Metabolism Congenital hypothyroidism Pendred syndrome SLC26A4 gene mutations China |
author_facet |
Chunyun Fu Haiyang Zheng Shujie Zhang Yun Chen Jiasun Su Jin Wang Bobo Xie Xuyun Hu Xin Fan Jingsi Luo Chuan Li Rongyu Chen Yiping Shen Shaoke Chen |
author_sort |
Chunyun Fu |
title |
Mutation screening of the SLC26A4 gene in a cohort of 192 Chinese patients with congenital hypothyroidism |
title_short |
Mutation screening of the SLC26A4 gene in a cohort of 192 Chinese patients with congenital hypothyroidism |
title_full |
Mutation screening of the SLC26A4 gene in a cohort of 192 Chinese patients with congenital hypothyroidism |
title_fullStr |
Mutation screening of the SLC26A4 gene in a cohort of 192 Chinese patients with congenital hypothyroidism |
title_full_unstemmed |
Mutation screening of the SLC26A4 gene in a cohort of 192 Chinese patients with congenital hypothyroidism |
title_sort |
mutation screening of the slc26a4 gene in a cohort of 192 chinese patients with congenital hypothyroidism |
publisher |
Brazilian Society of Endocrinology and Metabolism |
series |
Archives of Endocrinology and Metabolism |
issn |
2359-4292 |
publishDate |
2016-02-01 |
description |
ABSTRACT Objective Pendred syndrome (PS) is an autosomal recessive disorder characterised by sensorineural hearing loss and thyroid dyshormonogenesis. It is caused by biallelic mutations in the SLC26A4 gene encoding for pendrin. Hypothyroidism in PS can be present from birth and therefore diagnosed by neonatal screening. The aim of this study was to examine the SLC26A4 mutation spectrum and prevalence among congenital hypothyroidism (CH) patients in the Guangxi Zhuang Autonomous Region of China and to establish how frequently PS causes hearing impairment in our patients with CH. Subjects and methods Blood samples were collected from 192 CH patients in Guangxi Zhuang Autonomous Region, China, and genomic DNA was extracted from peripheral blood leukocytes. All exons of the SLC26A4 gene together with their exon-intron boundaries were screened by next-generation sequencing. Patients with SLC26A4 mutations underwent a complete audiological evaluation including otoscopic examination, audiometry and morphological evaluation of the inner ear. Results Next generation sequencing analysis of SLC26A4 in 192 CH patients revealed five different heterozygous variations in eight individuals (8/192, 4%). The prevalence of SLC26A4 mutations was 4% among studied Chinese CH. Three of the eight were diagnosed as enlargement of the vestibular aqueduct (EVA), no PS were found in our 192 CH patients. The mutations included one novel missense variant p.P469S, as well as four known missense variants, namely p.V233L, p.M147I, p.V609G and p.D661E. Of the eight patients identified with SLC26A4 variations in our study, seven patients showed normal size/location of thyroid gland, and one patients showed a decreased size one. Conclusions The prevalence of SLC26A4 pathogenic variants was 4% among studied Chinese patients with CH. Our study expanded the SLC26A4 mutation spectrum, provided the best estimation of SLC26A4 mutation rate for Chinese CH patients and indicated the rarity of PS as a cause of CH. |
topic |
Congenital hypothyroidism Pendred syndrome SLC26A4 gene mutations China |
url |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972016000400323&lng=en&tlng=en |
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