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Whole-exome sequencing identified a novel heterozygous mutation of SALL1 and a new homozygous mutation of PTPRQ in a Chinese family with Townes-Brocks syndrome and hearing loss

BACKGROUND: Previous studies have revealed that mutations of Spalt Like Transcription Factor 1 (SALL1) are responsible for Townes-Brocks syndrome (TBS), a rare genetic disorder that is characterized by an imperforate anus, dysplastic ears, thumb malformations and other abnormalities, such as hearing...

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Autores principales: Yang, Guangxian, Yin, Yi, Tan, Zhiping, Liu, Jian, Deng, Xicheng, Yang, Yifeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819242/
https://www.ncbi.nlm.nih.gov/pubmed/33478437
http://dx.doi.org/10.1186/s12920-021-00871-9
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author Yang, Guangxian
Yin, Yi
Tan, Zhiping
Liu, Jian
Deng, Xicheng
Yang, Yifeng
author_facet Yang, Guangxian
Yin, Yi
Tan, Zhiping
Liu, Jian
Deng, Xicheng
Yang, Yifeng
author_sort Yang, Guangxian
collection PubMed
description BACKGROUND: Previous studies have revealed that mutations of Spalt Like Transcription Factor 1 (SALL1) are responsible for Townes-Brocks syndrome (TBS), a rare genetic disorder that is characterized by an imperforate anus, dysplastic ears, thumb malformations and other abnormalities, such as hearing loss, foot malformations, renal impairment with or without renal malformations, genitourinary malformations, and congenital heart disease. In addition, the protein tyrosine phosphatase receptor type Q (PTPRQ) gene has been identified in nonsyndromic hearing loss patients with autosomal recessive or autosomal dominant inherited patterns. METHODS: A Chinese family with TBS and hearing loss was enrolled in this study. The proband was a two-month-old girl who suffered from congenital anal atresia with rectal perineal fistula, ventricular septal defect, patent ductus arteriosus, pulmonary hypertension (PH), and finger deformities. The proband’s father also had external ear deformity with deafness, toe deformities and PH, although his anus was normal. Further investigation found that the proband’s mother presented nonsyndromic hearing loss, and the proband’s mother’s parents were consanguine married. Whole-exome sequencing and Sanger sequencing were applied to detect the genetic lesions of TBS and nonsyndromic hearing loss. RESULTS: Via whole-exome sequencing and Sanger sequencing of the proband and her mother, we identified a novel heterozygous mutation (ENST00000251020: c.1428_1429insT, p. K478QfsX38) of SALL1 in the proband and her father who presented TBS phenotypes, and we also detected a new homozygous mutation [ENST00000266688: c.1057_1057delC, p. L353SfsX8)] of PTPRQ in the proband’s mother and uncle, who suffered from nonsyndromic hearing loss. Both mutations were located in the conserved sites of the respective protein and were predicted to be deleterious by informatics analysis. CONCLUSIONS: This study confirmed the diagnosis of TBS at the molecular level and expanded the spectrum of SALL1 mutations and PTPRQ mutations. Our study may contribute to the clinical management and genetic counselling of TBS and hearing loss.
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spelling pubmed-78192422021-01-22 Whole-exome sequencing identified a novel heterozygous mutation of SALL1 and a new homozygous mutation of PTPRQ in a Chinese family with Townes-Brocks syndrome and hearing loss Yang, Guangxian Yin, Yi Tan, Zhiping Liu, Jian Deng, Xicheng Yang, Yifeng BMC Med Genomics Research Article BACKGROUND: Previous studies have revealed that mutations of Spalt Like Transcription Factor 1 (SALL1) are responsible for Townes-Brocks syndrome (TBS), a rare genetic disorder that is characterized by an imperforate anus, dysplastic ears, thumb malformations and other abnormalities, such as hearing loss, foot malformations, renal impairment with or without renal malformations, genitourinary malformations, and congenital heart disease. In addition, the protein tyrosine phosphatase receptor type Q (PTPRQ) gene has been identified in nonsyndromic hearing loss patients with autosomal recessive or autosomal dominant inherited patterns. METHODS: A Chinese family with TBS and hearing loss was enrolled in this study. The proband was a two-month-old girl who suffered from congenital anal atresia with rectal perineal fistula, ventricular septal defect, patent ductus arteriosus, pulmonary hypertension (PH), and finger deformities. The proband’s father also had external ear deformity with deafness, toe deformities and PH, although his anus was normal. Further investigation found that the proband’s mother presented nonsyndromic hearing loss, and the proband’s mother’s parents were consanguine married. Whole-exome sequencing and Sanger sequencing were applied to detect the genetic lesions of TBS and nonsyndromic hearing loss. RESULTS: Via whole-exome sequencing and Sanger sequencing of the proband and her mother, we identified a novel heterozygous mutation (ENST00000251020: c.1428_1429insT, p. K478QfsX38) of SALL1 in the proband and her father who presented TBS phenotypes, and we also detected a new homozygous mutation [ENST00000266688: c.1057_1057delC, p. L353SfsX8)] of PTPRQ in the proband’s mother and uncle, who suffered from nonsyndromic hearing loss. Both mutations were located in the conserved sites of the respective protein and were predicted to be deleterious by informatics analysis. CONCLUSIONS: This study confirmed the diagnosis of TBS at the molecular level and expanded the spectrum of SALL1 mutations and PTPRQ mutations. Our study may contribute to the clinical management and genetic counselling of TBS and hearing loss. BioMed Central 2021-01-21 /pmc/articles/PMC7819242/ /pubmed/33478437 http://dx.doi.org/10.1186/s12920-021-00871-9 Text en © The Author(s) 2021, corrected publication 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Yang, Guangxian
Yin, Yi
Tan, Zhiping
Liu, Jian
Deng, Xicheng
Yang, Yifeng
Whole-exome sequencing identified a novel heterozygous mutation of SALL1 and a new homozygous mutation of PTPRQ in a Chinese family with Townes-Brocks syndrome and hearing loss
title Whole-exome sequencing identified a novel heterozygous mutation of SALL1 and a new homozygous mutation of PTPRQ in a Chinese family with Townes-Brocks syndrome and hearing loss
title_full Whole-exome sequencing identified a novel heterozygous mutation of SALL1 and a new homozygous mutation of PTPRQ in a Chinese family with Townes-Brocks syndrome and hearing loss
title_fullStr Whole-exome sequencing identified a novel heterozygous mutation of SALL1 and a new homozygous mutation of PTPRQ in a Chinese family with Townes-Brocks syndrome and hearing loss
title_full_unstemmed Whole-exome sequencing identified a novel heterozygous mutation of SALL1 and a new homozygous mutation of PTPRQ in a Chinese family with Townes-Brocks syndrome and hearing loss
title_short Whole-exome sequencing identified a novel heterozygous mutation of SALL1 and a new homozygous mutation of PTPRQ in a Chinese family with Townes-Brocks syndrome and hearing loss
title_sort whole-exome sequencing identified a novel heterozygous mutation of sall1 and a new homozygous mutation of ptprq in a chinese family with townes-brocks syndrome and hearing loss
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819242/
https://www.ncbi.nlm.nih.gov/pubmed/33478437
http://dx.doi.org/10.1186/s12920-021-00871-9
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