Identification and functional analysis of a novel mutation in the SOX10 gene associated with Waardenburg syndrome type IV

Wang, Hong-Han; Chen, Hongsheng; Li, Haibo; Zhang, Hua; Mei, Lingyun; He, Chufeng; Wang, Xingwei; Men, Meichao; Jiang, Lu; Liao, Xin; Wu, Hong

doi:10.1016/j.gene.2014.01.026

Cited by 17 publications

(7 citation statements)

References 37 publications

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“…, a flow diagram of the search process is depicted. Out of the 246 potentially eligible articles based on title and abstract, 73 articles met the inclusion criteria and were included in the analysis . One article fulfilled the inclusion criteria, but was not included in the analysis because the patient suffered from a second genetic disorder that could as well result in HL .…”

Section: Resultsmentioning

confidence: 99%

Hearing loss in Waardenburg syndrome: a systematic review

et al. 2015

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Waardenburg syndrome (WS) is a rare genetic disorder characterized by hearing loss (HL) and pigment disturbances of hair, skin and iris. Classifications exist based on phenotype and genotype. The auditory phenotype is inconsistently reported among the different Waardenburg types and causal genes, urging the need for an up-to-date literature overview on this particular topic. We performed a systematic review in search for articles describing auditory features in WS patients along with the associated genotype. Prevalences of HL were calculated and correlated with the different types and genes of WS. Seventy-three articles were included, describing 417 individual patients. HL was found in 71.0% and was predominantly bilateral and sensorineural. Prevalence of HL among the different clinical types significantly differed (WS1: 52.3%, WS2: 91.6%, WS3: 57.1%, WS4: 83.5%). Mutations in SOX10 (96.5%), MITF (89.6%) and SNAI2 (100%) are more frequently associated with hearing impairment than other mutations. Of interest, the distinct disease-causing genes are able to better predict the auditory phenotype compared with different clinical types of WS. Consequently, it is important to confirm the clinical diagnosis of WS with molecular analysis in order to optimally inform patients about the risk of HL.

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Section: Resultsmentioning

confidence: 99%

Hearing loss in Waardenburg syndrome: a systematic review

et al. 2015

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“…Human embryonic kidney 293T (HEK293T) cells [ 31 ], human cervical carcinoma HeLa cells [ 32 ] and NIH3T3 cells [ 30 , 31 ] were kindly provided by JD Li (State Key Laboratory of Medical Genetics of China). Human melanoma UACC903 cell lines were purchased from the University of Arizona Cancer Center [ 33 ].…”

Section: Methodsmentioning

confidence: 99%

LEF-1 Regulates Tyrosinase Gene Transcription In Vitro

et al. 2015

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TYR, DCT and MITF are three important genes involved in maintaining the mature phenotype and producing melanin; they therefore participate in neural crest cell development into melanocytes. Previous studies have revealed that the Wnt signaling factor lymphoid enhancer-binding factor (LEF-1) can enhance DCT and MITF gene expression. However, whether LEF-1 also affects TYR gene expression remains unclear. In the present study, we found that LEF-1 regulated TYR transcription in vitro. LEF-1 overexpression increased TYR gene promoter activity, whereas LEF-1 knockdown by RNA interference significantly decreased TYR expression. Moreover, the core GTTTGAT sequence (-56 to -50) within the TYR promoter is essential for the effect of LEF-1 on TYR expression, and chromatin immunoprecipitation (ChIP) assay indicated that endogenous LEF-1 interacts with the TYR promoter. In addition, we observed a synergistic transactivation of the TYR promoter by LEF-1 and MITF. These data suggest that Wnt signaling plays an important role in regulating melanocyte development and differentiation.

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“…Wang et al . 32 identified a c.1063C > T (p.Q355*) mutation in SOX10 in a family with WS4 and reported that the mutated SOX10 variant retained nuclear localization and DNA-binding capabilities comparable to those observed in wild-type SOX10 ; however, the mutated SOX10 variant was unable to activate transcription of MITF via its promoter and acted as a dominant-negative repressor as compared with activity associated with wild-type SOX10 7 33 . In this study, we detected a c.1333delT (p.Ser445Glnfs*57) mutation in SOX10 in a family with WS4, with the mutated SOX10 variant sharing sequence homology with only the N-terminal 444 amino acids of the wild-type protein.…”

Section: Discussionmentioning

confidence: 99%

“…WS4 is also known as Waardenburg-Shah syndrome (OMIM 277580) and is characterized by hearing loss, depigmentation, and aganglionic megacolon (Hirschsprung disease). WS4 includes three subtypes [WS4A–C (OMIM 277580, 613265, and 613266)] caused by mutations in EDNRB, EDN3 , and SOX10 , respectively 7 8 9 . Mutations in EDNRB and EDN3 are inherited in the autosomal recessive (AR) or autosomal dominant (AD) form, whereas the SOX10 mutation is inherited as AD 10 11 12 13 and found in ~50% of WS4 patients 1 6 , with >30 WS4-related mutations reported in the Human Gene Mutation Database.…”

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confidence: 99%

A de novo deletion mutation in SOX10 in a Chinese family with Waardenburg syndrome type 4

Wang

Zhu

Shen

et al. 2017

Sci Rep

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Waardenburg syndrome type 4 (WS4) or Waardenburg-Shah syndrome is a rare genetic disorder with a prevalence of <1/1,000,000 and characterized by the association of congenital sensorineural hearing loss, pigmentary abnormalities, and intestinal aganglionosis. There are three types of WS4 (WS4A–C) caused by mutations in endothelin receptor type B, endothelin 3, and SRY-box 10 (SOX10), respectively. This study investigated a genetic mutation in a Chinese family with one WS4 patient in order to improve genetic counselling. Genomic DNA was extracted, and mutation analysis of the three WS4 related genes was performed using Sanger sequencing. We detected a de novo heterozygous deletion mutation [c.1333delT (p.Ser445Glnfs*57)] in SOX10 in the patient; however, this mutation was absent in the unaffected parents and 40 ethnicity matched healthy controls. Subsequent phylogenetic analysis and three-dimensional modelling of the SOX10 protein confirmed that the c.1333delT heterozygous mutation was pathogenic, indicating that this mutation might constitute a candidate disease-causing mutation.

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Identification and functional analysis of a novel mutation in the SOX10 gene associated with Waardenburg syndrome type IV

Cited by 17 publications

References 37 publications

Hearing loss in Waardenburg syndrome: a systematic review

Hearing loss in Waardenburg syndrome: a systematic review

LEF-1 Regulates Tyrosinase Gene Transcription In Vitro

A de novo deletion mutation in SOX10 in a Chinese family with Waardenburg syndrome type 4

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