耳聋患儿的TECTA基因突变分析

Diagnosis and reproductive guidance for a couple carrying a novel c. 1893C>T mutation of the TECTA gene

目的 探讨1例耳聋患儿的分子遗传病因,为家系的遗传咨询和产前诊断提供依据。 方法 提取先证者外周血基因组,用芯片法富集纯化127种耳聋相关基因,以>100×测序深度进行二代测序,通过数据库分析比对,寻找致病突变。用Sanger测序法进一步验证疑似突变,排除二代测序错配误差。 结果 先证者TECTA基因发生c.1893C>A纯合突变,该突变使TECTA蛋白翻译提前终止,丧失功能;USH2A基因存在c.13010C>T和c.12790G>A复合杂合突变,前者疑似致病突变,后者临床意义不明。家系分析证实先证者的突变均遗传自父母。 结论 TECTA基因c.1893C>A纯合突变可能是先证者耳聋的主要原因,该位点遵循常染色体隐性遗传。

Objective To explore the molecular basis for an individual with postnatal deafness and provide genetic counseling for her family.Methods Following extraction of genomic DNA from peripheral blood samples, 127 genes associated with deafness were subjected to targeted capturing and next generation sequencing. Suspected mutation was verified by Sanger sequencing.Results The proband was found to carry a homozygous c. 1893C>A mutation in the TECTA gene, which is located in the tectorial membrane of inner ear and may cause premature termination of translation of TECTA protein. In addition, two heterozygous mutations, c. 13010C>T and c. 12790G>A, were found in the USH2A gene. Whilst the former is likely to be pathogenic, the latter has unknown clinical significance. Further analysis suggested that all three mutations have derived from the parents of the proband. Conclusion The homozygous c. 1893C>A mutation of the TECTA gene probably underlies the proband’s hearing loss which conformed to an autosomal recessive inheritance.