摘要目的:分析并揭示Perrault综合征患者的分子病因。方法:选取郑州大学第一附属医院2021年2月至2022年3月收治的2例以双耳重度感音神经性听力损失为特征的男性Perrault综合征患者，总结患者及其家系的临床表型及基因变异，应用全外显子测序（whole exome sequencing，WES）技术对先证者进行致病变异筛选，结合临床表型确定候选基因及致病位点，用Sanger测序法对先证者及其家系成员进行验证。结果:WES结果显示家系1的先证者存在 LARS2基因（NM_015340.4）c.1565C>A（p.Thr522Asn）和c.1079T>C（p.Ile360Thr）的复合杂合变异，c.1565C>A来自先证者母亲，c.1079T>C来自先证者父亲。其中，c.1565C>A为已报道的致病变异，c.1079T>C为新变异。家系2先证者携带 HARS2基因（NM_012208.4）c.1273C>T（p.Arg425Trp）和c.1403G>C（p.Gly468Ala）的复合杂合变异，c.1273C>T来自母亲，c.1403G>C来自父亲，c.1273C>T为新变异，c.1403G>C为已报道可能致病变异。参考美国医学遗传学与基因组学学会基因变异分类标准，上述变异分别评级为致病、意义未明、意义未明和可能致病。 结论:本研究扩大了 LARS2和 HARS2基因的突变谱，基因检测在综合征型耳聋的早期诊断中发挥着重要作用。

abstractsObjective:To investigate the molecular etiology of Perrault syndrome by analyzing the clinical phenotype and pathogenic gene variants of 2 male patients with bilateral severe sensorineural deafness.Methods:Two male patients with Perrault syndrome characterized by severe sensonrineual deafness adimitted to the First Affiliated Hospital of Zhengzhou University between February 2021 and March 2022 were selected, and the clinical phenotype and pathogenic gene variants of them and their family members were summarized. The whole exome sequencing technology was used to screen the pathogenic variants of the probands, and the candidate variants were determined by combining with clinical phenotype. The probands and their family members were verified by the Sanger sequencing method.Results:The whole exome sequencing results showed that the proband of family 1 had a compound heterozygous variants of the LARS2 (NM_015340.4) gene c.1565C>A (p.Thr522Asn) and c.1079T>C (p.Ile360Thr). The reported pathogenic variant c.1565C>A came from the mother, and the novel variant c.1079T>C came from the father. The second proband harbored compound heterozygous variants of HARS2 gene (NM_012208.4) c.1273C>T (p.Arg425Trp) and c.1403G>C (p.Gly468Ala), with the former from the proband′s mother, the latter from the father. The c.1273C>T was novel and c.1403G>C was the reported pathogenic variant. All above variants were respectively classified as pathogenic, uncertain significance, uncertain significance and likely pathogenic based on the ACMG guidelines. Conclusion:This study expands the mutational spectrum of LARS2 and HARS2 genes, which highlights that genetic testing plays an important role in the early diagnosis of syndromic deafness.