PDF(Pubmed)
Abstract：
OBJECTIVE: To explore the molecular etiology of Waardenburg syndrome type II (WS2) in a family from Yunnan province, China.
METHODS: A total of 406 genes related to hereditary hearing loss were sequenced using next-generation sequencing. DNA samples were isolated from the peripheral blood DNA of probands. Those pathogenic mutations detected by next-generation sequencing in probands and their parents were validated by Sanger sequencing. The conservatism of variation sites in genes was also analyzed. The protein expression was detected by flow cytometry.
RESULTS: A heterozygous mutation c.178delG (p.D60fs*49) in the SOX10 gene was identified in the proband, which is a frameshift mutation and may cause protein loss of function and considered to be a pathogenic mutation. This was determined to be a de novo mutation because her family were demonstrated to be wild-type and symptom free. SOX10, FGFR3, SOX2, and PAX3 protein levels were reduced as determined by flow cytometry.
CONCLUSIONS: A novel frameshift mutation in SOX10 gene was identified in this study, which may be the cause of WS2 in proband. In addition, FGFR3, SOX2, and PAX3 might also participate in promoting the progression of WS2.
METHODS: A total of 406 genes related to hereditary hearing loss were sequenced using next-generation sequencing. DNA samples were isolated from the peripheral blood DNA of probands. Those pathogenic mutations detected by next-generation sequencing in probands and their parents were validated by Sanger sequencing. The conservatism of variation sites in genes was also analyzed. The protein expression was detected by flow cytometry.
RESULTS: A heterozygous mutation c.178delG (p.D60fs*49) in the SOX10 gene was identified in the proband, which is a frameshift mutation and may cause protein loss of function and considered to be a pathogenic mutation. This was determined to be a de novo mutation because her family were demonstrated to be wild-type and symptom free. SOX10, FGFR3, SOX2, and PAX3 protein levels were reduced as determined by flow cytometry.
CONCLUSIONS: A novel frameshift mutation in SOX10 gene was identified in this study, which may be the cause of WS2 in proband. In addition, FGFR3, SOX2, and PAX3 might also participate in promoting the progression of WS2.
摘要：
目的:探讨云南一家族Waardenburg综合征II型(WS2)的分子病因,中国。
方法：使用下一代测序对总共406个与遗传性听力损失相关的基因进行测序。从先证者的外周血DNA中分离DNA样品。通过下一代测序在先证者及其父母中检测到的致病性突变通过Sanger测序进行了验证。还分析了基因变异位点的保守性。通过流式细胞术检测蛋白表达。
结果：杂合突变c.178delG（p。在先证中鉴定了SOX10基因中的D60fs*49)，这是一种移码突变，可能导致蛋白质功能丧失，被认为是一种致病性突变。这被确定为从头突变，因为她的家人被证明是野生型且无症状。如通过流式细胞术确定的,S0X10、FGFR3、S0X2和PAX3蛋白水平降低。
结论：在这项研究中发现了SOX10基因的一个新的移码突变，这可能是WS2在先证者中的原因。此外,FGFR3、SOX2和PAX3也可能参与促进WS2的进展。
方法：使用下一代测序对总共406个与遗传性听力损失相关的基因进行测序。从先证者的外周血DNA中分离DNA样品。通过下一代测序在先证者及其父母中检测到的致病性突变通过Sanger测序进行了验证。还分析了基因变异位点的保守性。通过流式细胞术检测蛋白表达。
结果：杂合突变c.178delG（p。在先证中鉴定了SOX10基因中的D60fs*49)，这是一种移码突变，可能导致蛋白质功能丧失，被认为是一种致病性突变。这被确定为从头突变，因为她的家人被证明是野生型且无症状。如通过流式细胞术确定的,S0X10、FGFR3、S0X2和PAX3蛋白水平降低。
结论：在这项研究中发现了SOX10基因的一个新的移码突变，这可能是WS2在先证者中的原因。此外,FGFR3、SOX2和PAX3也可能参与促进WS2的进展。
