Abstract：
Hearing loss is the most frequent sensorineural disorder, affecting approximately 1:1000 newborns. Hereditary forms (HHL) represent 50-60% of cases, highlighting the relevance of genetic testing in deaf patients. HHL is classified as non-syndromic (NSHL-70% of cases) or syndromic (SHL-30% of cases). In this study, a multistep and integrative approach aimed at identifying the molecular cause of HHL in 102 patients, whose GJB2 analysis already showed a negative result, is described. In NSHL patients, multiplex ligation probe amplification and long-range PCR analyses of the STRC gene solved 13 cases, while whole exome sequencing (WES) identified the genetic diagnosis in 26 additional ones, with a total detection rate of 47.6%. Concerning SHL, WES detected the molecular cause in 55% of cases. Peculiar findings are represented by the identification of four subjects displaying a dual molecular diagnosis and eight affected by non-syndromic mimics, five of them presenting Usher syndrome type 2. Overall, this study provides a detailed characterisation of the genetic causes of HHL in the Italian population. Furthermore, we highlighted the frequency of Usher syndrome type 2 carriers in the Italian population to pave the way for a more effective implementation of diagnostic and follow-up strategies for this disease.
摘要：
听力损失是最常见的感觉神经性疾病,影响大约1:1000的新生儿。遗传性形式（HHL）占50-60％的病例，强调基因检测在聋哑患者中的相关性。HHL分为非综合征（NSHL-70％的病例）或综合征（SHL-30％的病例）。在这项研究中,一种多步骤的综合方法，旨在确定102例患者HHL的分子原因，其GJB2分析已经显示阴性结果，被描述。在NSHL患者中，STRC基因的多重连接探针扩增和远程PCR分析解决了13例，而整个外显子组测序（WES）在另外26个基因中确定了遗传诊断，总检出率为47.6%。关于SHL,WES在55％的病例中检测到分子原因。特殊的发现由四个显示双重分子诊断的受试者和八个受非综合征模拟物影响的受试者的鉴定代表。其中5人表现为Usher综合征2型.总的来说,这项研究提供了意大利人群中HHL遗传原因的详细描述.此外，我们强调了意大利人群中Usher综合征2型携带者的频率,为更有效地实施该疾病的诊断和随访策略铺平道路.
