Objective To reveal the genetic pathogenesis of the probands with enlarged vestibular aqueduct syndrome(EVAS)in two hearing loss pedigrees.Methods Target next generation sequencing(TNGS)technology was used to screen the cause of disease in two probands,and determine candidate genes that may cause disease in combination with clinical pheno-types.Multiplex ligation-dependent probe amplification(MLPA)and Sanger sequencing method were applied to verify the copy number variations and base variations of probands and their pedigree members.Results TNGS technology found com-pound heterozygous mutation of EX13_EX15DEL and c.919-2A＞G in SLC26A4 gene in probands of pedigree 1.MLPA and Sanger sequencing verified these two variations and suggested that EX13_EX15DEL was inherited from his healthy mother and c.919-2A＞G was inherited from his healthy father.Homozygous variation of SLC26A4 EX5_EX6DEL was identified in proband of pedigree 2.MLPA confirmed the deletion and showed that SLC26A4 EX5_EX6DEL homozygous variation was inherited from his prarents.After searching the human mutation databases and the related references,the two deletions are unreported copy number variations(CNVs).Conclusion The CNVs of SLC26A4 genes EX5_EX6DEL and EX13_EX15DEL are the causes of the disease in theses two pedigrees.SLC26A4 CNVs are important pathogenic factors in EVAS patients with heterozygous or no variation of SLC26A4 gene.It is necessary to strengthen the screening of CNVs of SLC26A4 gene in these patients.
enlarged vestibular aqueduct syndrome(EVAS)SLC26A4 genecopy number variation(CNV)target next generation sequencing(TNGS)
NETL
NSTL
万方数据
