Abstract：
Hearing loss (HL) is the most common sensory impairment, and it is characterized by a high clinical/genetic heterogeneity. Here we report the identification of dual molecular diagnoses (i.e., mutations at two loci that lead to the expression of two Mendelian conditions) in a series of families affected by non-syndromic and syndromic HL. Eighty-two patients who displayed HL as a major clinical feature have been recruited during the last year. After an accurate clinical evaluation, individuals have been analyzed through whole-exome sequencing (WES). This protocol led to the identification of seven families characterized by the presence of a dual diagnosis. In particular, based on the clinical and genetic findings, patients have been classified into two groups: (a) patients with HL and distinct phenotypes not fitting in a known syndrome due to mutations at two loci (e.g., HL in association with Marfan syndrome) and (b) patients with two genes involved in HL phenotype (e.g., TMPRSS3 and MYH14). These data highlight for the first time the high prevalence of dual molecular diagnoses in HL patients and suggest that they should be considered especially for those cases that depart from the expected clinical manifestation or those characterized by a significant intra-familiar variability.
摘要：
听力损失（HL）是最常见的感觉障碍，其特点是具有较高的临床/遗传异质性。在这里，我们报告了双分子诊断的鉴定(即，导致两个孟德尔条件表达的两个基因座的突变）在一系列受非综合征性和综合征性HL影响的家庭中。去年招募了82名表现为主要临床特征的HL患者。经过准确的临床评估，通过全外显子组测序(WES)对个体进行了分析.该方案导致了以双重诊断为特征的七个家族的鉴定。特别是,根据临床和遗传发现，患者已分为两组：（a）由于两个基因座的突变，HL和不同表型不符合已知综合征的患者（例如，与马凡氏综合征相关的HL)和(b)具有两个参与HL表型的基因的患者(例如，TMPRSS3和MYH14）。这些数据首次强调了HL患者双分子诊断的高患病率，并建议尤其是对于那些偏离预期临床表现或具有明显的内部熟悉变异性的病例，应将其考虑在内。
