New Genotypes and Phenotypes in Patients with 3 Subtypes of Waardenburg Syndrome Identified by Diagnostic Next-Generation Sequencing
Background. Waardenburg syndrome (WS) is one of the most common forms of syndromic deafness with heterogeneity of loci and alleles and variable expressivity of clinical features. Methods. The technology of single-nucleotide variants (SNV) and copy number variation (CNV) detection was developed to in...
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Wiley
2019-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2019/7143458 |
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| author | Wu Li Lingyun Mei Hongsheng Chen Xinzhang Cai Yalan Liu Meichao Men Xue Zhong Liu Denise Yan Jie Ling Yong Feng |
| author_facet | Wu Li Lingyun Mei Hongsheng Chen Xinzhang Cai Yalan Liu Meichao Men Xue Zhong Liu Denise Yan Jie Ling Yong Feng |
| author_sort | Wu Li |
| collection | DOAJ |
| description | Background. Waardenburg syndrome (WS) is one of the most common forms of syndromic deafness with heterogeneity of loci and alleles and variable expressivity of clinical features. Methods. The technology of single-nucleotide variants (SNV) and copy number variation (CNV) detection was developed to investigate the genotype spectrum of WS in a Chinese population. Results. Ninety WS patients and 24 additional family members were recruited for the study. Fourteen mutations had not been previously reported, including c.808C>G, c.117C>A, c.152T>G, c.803G>T, c.793-3T >G, and c.801delT on PAX3; c.642_650delAAG on MITF; c.122G>T and c.127C>T on SOX10; c.230C>G and c.365C>T on SNAI2; and c.481A>G, c.1018C>G, and c.1015C>T on EDNRB. Three CNVs were de novo and first reported in our study. Five EDNRB variants were associated with WS type 1 in the heterozygous state for the first time, with a detection rate of 22.2%. Freckles occur only in WS type 2. Yellow hair, amblyopia, congenital ptosis, narrow palpebral fissures, and pigmentation spots are rare and unique symptoms in WS patients from China. Conclusions. EDNRB should be considered as another prevalent pathogenic gene in WS type 1. Our study expanded the genotype and phenotype spectrum of WS, and diagnostic next-generation sequencing is promising for WS. |
| format | Article |
| id | doaj-art-b8e1cc6bd7974fbf82eef0a2e5546ad1 |
| institution | DOAJ |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-b8e1cc6bd7974fbf82eef0a2e5546ad12025-08-20T03:22:48ZengWileyNeural Plasticity2090-59041687-54432019-01-01201910.1155/2019/71434587143458New Genotypes and Phenotypes in Patients with 3 Subtypes of Waardenburg Syndrome Identified by Diagnostic Next-Generation SequencingWu Li0Lingyun Mei1Hongsheng Chen2Xinzhang Cai3Yalan Liu4Meichao Men5Xue Zhong Liu6Denise Yan7Jie Ling8Yong Feng9Department of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, ChinaDepartment of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, ChinaDepartment of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, ChinaDepartment of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, ChinaDepartment of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, ChinaHealth Management Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, ChinaDepartment of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, ChinaDepartment of Otolaryngology, University of Miami, Miller School of Medicine, Miami, USADepartment of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, ChinaDepartment of Otolaryngology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, ChinaBackground. Waardenburg syndrome (WS) is one of the most common forms of syndromic deafness with heterogeneity of loci and alleles and variable expressivity of clinical features. Methods. The technology of single-nucleotide variants (SNV) and copy number variation (CNV) detection was developed to investigate the genotype spectrum of WS in a Chinese population. Results. Ninety WS patients and 24 additional family members were recruited for the study. Fourteen mutations had not been previously reported, including c.808C>G, c.117C>A, c.152T>G, c.803G>T, c.793-3T >G, and c.801delT on PAX3; c.642_650delAAG on MITF; c.122G>T and c.127C>T on SOX10; c.230C>G and c.365C>T on SNAI2; and c.481A>G, c.1018C>G, and c.1015C>T on EDNRB. Three CNVs were de novo and first reported in our study. Five EDNRB variants were associated with WS type 1 in the heterozygous state for the first time, with a detection rate of 22.2%. Freckles occur only in WS type 2. Yellow hair, amblyopia, congenital ptosis, narrow palpebral fissures, and pigmentation spots are rare and unique symptoms in WS patients from China. Conclusions. EDNRB should be considered as another prevalent pathogenic gene in WS type 1. Our study expanded the genotype and phenotype spectrum of WS, and diagnostic next-generation sequencing is promising for WS.http://dx.doi.org/10.1155/2019/7143458 |
| spellingShingle | Wu Li Lingyun Mei Hongsheng Chen Xinzhang Cai Yalan Liu Meichao Men Xue Zhong Liu Denise Yan Jie Ling Yong Feng New Genotypes and Phenotypes in Patients with 3 Subtypes of Waardenburg Syndrome Identified by Diagnostic Next-Generation Sequencing Neural Plasticity |
| title | New Genotypes and Phenotypes in Patients with 3 Subtypes of Waardenburg Syndrome Identified by Diagnostic Next-Generation Sequencing |
| title_full | New Genotypes and Phenotypes in Patients with 3 Subtypes of Waardenburg Syndrome Identified by Diagnostic Next-Generation Sequencing |
| title_fullStr | New Genotypes and Phenotypes in Patients with 3 Subtypes of Waardenburg Syndrome Identified by Diagnostic Next-Generation Sequencing |
| title_full_unstemmed | New Genotypes and Phenotypes in Patients with 3 Subtypes of Waardenburg Syndrome Identified by Diagnostic Next-Generation Sequencing |
| title_short | New Genotypes and Phenotypes in Patients with 3 Subtypes of Waardenburg Syndrome Identified by Diagnostic Next-Generation Sequencing |
| title_sort | new genotypes and phenotypes in patients with 3 subtypes of waardenburg syndrome identified by diagnostic next generation sequencing |
| url | http://dx.doi.org/10.1155/2019/7143458 |
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