Mutations in the CDC14A (Cell Division-Cycle 14A) gene, which encodes a conserved dual-specificity protein tyrosine phosphatase, have been identified as a cause of autosomal recessive non-syndromic hearing loss (DFNB32) and hearing impairment infertility male syndrome (HIIMS). We used next-generation sequencing to screen six deaf probands from six families segregating sensorineural moderate-to-profound hearing loss. Data analysis and variant prioritization were completed using a custom bioinformatics pipeline. We identified three homozygous loss of function variants (p.Arg345Ter, p.Arg376Ter, and p.Ala451Thrfs*43) in the CDC14A gene, segregating with deafness in each family. Of the six families, four segregated the p.Arg376Ter mutation, one family segregated the p.Arg345Ter mutation and one family segregated a novel frameshift (p.Ala451Thrfs*43) mutation. In-depth phenotyping of affected individuals ruled out secondary syndromic findings. This study implicates the p.Arg376Ter mutation might be as a founder mutation in the Iranian population. It also provides the first semen analysis for deaf males carrying mutations in exon 11 of CDC14A and reveals a genotype–phenotype correlation that delineates between DFNB32 and HIIMS. The clinical results from affected males suggest the NM_033313.2 transcript alone is sufficient for proper male fertility, but not for proper auditory function. We conclude that DFNB32 is a distinct phenotypic entity in males.

编码保守的双特异性蛋白酪氨酸磷酸酶的CDC14A（细胞分裂周期14A）基因突变已被鉴定为常染色体隐性非综合征性听力损失（DFNB32）和听力障碍性不育男性综合征（HIIMS）的原因。我们使用了下一代测序技术来筛查六个家族的六个聋人先证者，他们将感觉神经性中度至深度听力损失分开。使用定制的生物信息学管道完成了数据分析和变量优先级划分。我们确定的功能变型有三种纯合子损失（p.Arg345Ter，p.Arg376Ter和p.Ala451Thrfs * 43）在CDC14A基因，每个家庭都与耳聋相分离。在这六个家族中，四个家族分离了p.Arg376Ter突变，一个家族分离了p.Arg345Ter突变，一个家族分离了新的移码（p.Ala451Thrfs * 43）突变。受影响个体的深入表型排除了继发综合征的发现。这项研究暗示p.Arg376Ter突变可能是伊朗人群中的奠基人突变。它还为患有CDC14A外显子11突变的聋哑男性提供了首次精液分析。并揭示了在DFNB32和HIIMS之间划定的基因型与表型的相关性。受影响男性的临床结果表明，仅NM_033313.2转录本足以实现适当的男性生育能力，但不足以实现适当的听觉功能。我们得出的结论是，DFNB32是男性中独特的表型实体。