Analysis of genetic characteristics in two Chinese children of type Ⅱ Waardenburg syndrome.
10.3760/cma.j.cn115330-20200121-00041
- Author:
Jing MA
1
;
Cheng MING
2
;
Ken LIN
2
;
Li Ping ZHAO
2
;
Xian Yun BI
2
;
Guo LI
2
;
Tie Song ZHANG
3
;
Biao RUAN
4
,
5
Author Information
1. Department of Otorhinolaryngology Head Neck Surgery, Kunming Children's Hospital, Kunming 650228, China Kunming Key Laboratory for Prevention and Control of Congenital Birth Defects of Children, Kunming 650228, China.
2. Department of Otorhinolaryngology Head Neck Surgery, Kunming Children's Hospital, Kunming 650228, China.
3. Department of Otorhinolaryngology Head Neck Surgery, Kunming Children's Hospital, Kunming 650228, China Yunnan Key Laboratory of Children's Major Disease Research, Kunming 650228, China.
4. Department of Otorhinolaryngology, the First Hospital of Kunming Medical University, Kunming 650032, China
5. Ma Jing and Ming Cheng contributed equally to this article.
- Publication Type:Journal Article
- MeSH:
Asians/genetics*;
Child;
China;
Humans;
Mutation;
Pedigree;
SOXE Transcription Factors/genetics*;
Waardenburg Syndrome/genetics*
- From:
Chinese Journal of Otorhinolaryngology Head and Neck Surgery
2021;56(1):47-54
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To screen and analyze the mutations of MITF gene in two children of type Ⅱ Waardenburg syndrome (WS2) from different families in Yunnan,China,and to explore the possible molecular pathogenesis. Methods: With informed consent, medical history collection, physical examinations, audiological evaluation, and high resolution computer tomography (HRCT) scan of temporal bone were performed on the two WS2 probands and their family members. Genomic DNA was extracted from peripheral blood of all individuals. The coding regions including all exons, part of introns and promoters of MITF, PAX3, SOX10, SNAI2, END3, ENDRB, and KITLG genes were sequenced by high-throughput sequencing. According to the results of high-throughput sequencing, pathogenic mutations detected in the probands and their parents were verified by Sanger sequencing. Results: The proband 1 carried c.641_643delGAA mutation in the 7th exon of MITF gene, which was a frame-shift mutation resulting in an amino acid change of p.214delR. It was a de novo mutation as the parents of proband 1 showed no variation on this site. The proband 2 carried heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene, which defected the function of MITF protein. Conclusion: Genetic examinations provide important evidence for diagnosis of Waardenburg syndrome. Heterozygous mutation c.641_643delGAA and heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene might be the molecular pathogenesis of the two WS2 probands in this study.
