Two novel mutations of PAX3 and SOX10 were characterized as genetic causes of Waardenburg Syndrome
Abstract Background The objective of this study was to investigate the genetic causes of two probands diagnosed as Waardenburg syndrome (WS type I and IV) from two unrelated Chinese families. Methods PAX3 and SOX10 were the main pathogenic genes for WS type I (WS I) and IV (WS IV), respectively; all...
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Format: | Article |
Language: | English |
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Wiley
2020-05-01
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Series: | Molecular Genetics & Genomic Medicine |
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Online Access: | https://doi.org/10.1002/mgg3.1217 |
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doaj-34f10dce6e674dd89166d290fa66f5db |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yongbo Yu Wei Liu Min Chen Yang Yang Yeran Yang Enyu Hong Jie Lu Jun Zheng Xin Ni Yongli Guo Jie Zhang |
spellingShingle |
Yongbo Yu Wei Liu Min Chen Yang Yang Yeran Yang Enyu Hong Jie Lu Jun Zheng Xin Ni Yongli Guo Jie Zhang Two novel mutations of PAX3 and SOX10 were characterized as genetic causes of Waardenburg Syndrome Molecular Genetics & Genomic Medicine hearing loss PAX3 SOX10 Waardenburg syndrome |
author_facet |
Yongbo Yu Wei Liu Min Chen Yang Yang Yeran Yang Enyu Hong Jie Lu Jun Zheng Xin Ni Yongli Guo Jie Zhang |
author_sort |
Yongbo Yu |
title |
Two novel mutations of PAX3 and SOX10 were characterized as genetic causes of Waardenburg Syndrome |
title_short |
Two novel mutations of PAX3 and SOX10 were characterized as genetic causes of Waardenburg Syndrome |
title_full |
Two novel mutations of PAX3 and SOX10 were characterized as genetic causes of Waardenburg Syndrome |
title_fullStr |
Two novel mutations of PAX3 and SOX10 were characterized as genetic causes of Waardenburg Syndrome |
title_full_unstemmed |
Two novel mutations of PAX3 and SOX10 were characterized as genetic causes of Waardenburg Syndrome |
title_sort |
two novel mutations of pax3 and sox10 were characterized as genetic causes of waardenburg syndrome |
publisher |
Wiley |
series |
Molecular Genetics & Genomic Medicine |
issn |
2324-9269 |
publishDate |
2020-05-01 |
description |
Abstract Background The objective of this study was to investigate the genetic causes of two probands diagnosed as Waardenburg syndrome (WS type I and IV) from two unrelated Chinese families. Methods PAX3 and SOX10 were the main pathogenic genes for WS type I (WS I) and IV (WS IV), respectively; all coding exons of these genes were sequenced on the two probands and their family members. Luciferase reporter assay and co‐immunoprecipitation (CO‐IP) were conducted to verify potential functional outcomes of the novel mutations. Results The first proband is a 9 years old girl diagnosed with WS I. A novel PAX3 heterozygous mutation of c.372‐373delGA (p.N125fs) was identified, which results in a frameshift and truncation of PAX3 protein. In family II, a 2 years old girl was diagnosed with WS IV, and Sanger sequencing revealed a de novo SOX10 mutation of c.1114insTGGGGCCCCCACACTACACCGAC (p.Q372fs), a frameshift mutation that extends the amino acid chain of SOX10 protein. Functional studies indicated that the novel mutation of SOX10 had no effects on the interaction of SOX10 and PAX3, but reduced transactivate capacity of melanocyte inducing transcription factor (MITF) promoter. Both PAX3 and SOX10 mutation‐induced defects of MITF transcription might contribute to the WS pathogenesis. Conclusion We revealed a novel mutation in PAX3 and a de novo mutation in SOX10, which might account for the underlying pathogenesis of WS. This study expands the database of both PAX10 and PAX3 mutations and improves our understanding of the causes of WS. |
topic |
hearing loss PAX3 SOX10 Waardenburg syndrome |
url |
https://doi.org/10.1002/mgg3.1217 |
work_keys_str_mv |
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doaj-34f10dce6e674dd89166d290fa66f5db2020-11-25T02:09:51ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-05-0185n/an/a10.1002/mgg3.1217Two novel mutations of PAX3 and SOX10 were characterized as genetic causes of Waardenburg SyndromeYongbo Yu0Wei Liu1Min Chen2Yang Yang3Yeran Yang4Enyu Hong5Jie Lu6Jun Zheng7Xin Ni8Yongli Guo9Jie Zhang10Beijing Key Laboratory for Pediatric Diseases of Otolaryngology Head and Neck Surgery Beijing Pediatric Research Institute Beijing Children’s Hospital Capital Medical University National Center for Children's Health (NCCH) Beijing ChinaDepartment of Otolaryngology, Head and Neck Surgery Beijing Children’s Hospital Capital Medical University National Center for Children's Health (NCCH) Beijing ChinaDepartment of Otolaryngology, Head and Neck Surgery Beijing Children’s Hospital Capital Medical University National Center for Children's Health (NCCH) Beijing ChinaDepartment of Otolaryngology, Head and Neck Surgery Beijing Children’s Hospital Capital Medical University National Center for Children's Health (NCCH) Beijing ChinaBeijing Key Laboratory for Pediatric Diseases of Otolaryngology Head and Neck Surgery Beijing Pediatric Research Institute Beijing Children’s Hospital Capital Medical University National Center for Children's Health (NCCH) Beijing ChinaBeijing Key Laboratory for Pediatric Diseases of Otolaryngology Head and Neck Surgery Beijing Pediatric Research Institute Beijing Children’s Hospital Capital Medical University National Center for Children's Health (NCCH) Beijing ChinaBeijing Key Laboratory for Pediatric Diseases of Otolaryngology Head and Neck Surgery Beijing Pediatric Research Institute Beijing Children’s Hospital Capital Medical University National Center for Children's Health (NCCH) Beijing ChinaDepartment of Otolaryngology, Head and Neck Surgery Beijing Children’s Hospital Capital Medical University National Center for Children's Health (NCCH) Beijing ChinaDepartment of Otolaryngology, Head and Neck Surgery Beijing Children’s Hospital Capital Medical University National Center for Children's Health (NCCH) Beijing ChinaBeijing Key Laboratory for Pediatric Diseases of Otolaryngology Head and Neck Surgery Beijing Pediatric Research Institute Beijing Children’s Hospital Capital Medical University National Center for Children's Health (NCCH) Beijing ChinaDepartment of Otolaryngology, Head and Neck Surgery Beijing Children’s Hospital Capital Medical University National Center for Children's Health (NCCH) Beijing ChinaAbstract Background The objective of this study was to investigate the genetic causes of two probands diagnosed as Waardenburg syndrome (WS type I and IV) from two unrelated Chinese families. Methods PAX3 and SOX10 were the main pathogenic genes for WS type I (WS I) and IV (WS IV), respectively; all coding exons of these genes were sequenced on the two probands and their family members. Luciferase reporter assay and co‐immunoprecipitation (CO‐IP) were conducted to verify potential functional outcomes of the novel mutations. Results The first proband is a 9 years old girl diagnosed with WS I. A novel PAX3 heterozygous mutation of c.372‐373delGA (p.N125fs) was identified, which results in a frameshift and truncation of PAX3 protein. In family II, a 2 years old girl was diagnosed with WS IV, and Sanger sequencing revealed a de novo SOX10 mutation of c.1114insTGGGGCCCCCACACTACACCGAC (p.Q372fs), a frameshift mutation that extends the amino acid chain of SOX10 protein. Functional studies indicated that the novel mutation of SOX10 had no effects on the interaction of SOX10 and PAX3, but reduced transactivate capacity of melanocyte inducing transcription factor (MITF) promoter. Both PAX3 and SOX10 mutation‐induced defects of MITF transcription might contribute to the WS pathogenesis. Conclusion We revealed a novel mutation in PAX3 and a de novo mutation in SOX10, which might account for the underlying pathogenesis of WS. This study expands the database of both PAX10 and PAX3 mutations and improves our understanding of the causes of WS.https://doi.org/10.1002/mgg3.1217hearing lossPAX3SOX10Waardenburg syndrome |