The CDC14A gene was first associated with autosomal recessive hearing impairment and infertile male syndrome (HIIMS) in 2017 (Imtiaz et al., PMID: 29293958). In five families reported with HIIMS, females homozygous for CDC14A variants had prelingual sensorineural hearing loss, and homozygous males had hearing loss and infertility (PMID: 29293958). Three families segregated truncating variants predicted to affect all isoforms of the gene. Two families had two different missense variants in the dual-specificity phosphatase domain of CDC14A. One additional family had a third missense variant in this domain, but the fertility status of the affected males could not be determined. This gene-disease relationship is supported by expression studies and animal models (PMIDs: 27259055, 29293958). There are four mouse models for this syndrome, including one with a predicted deleterious missense variant in the phosphatase domain generated by CRISPR/Cas9 (PMID: 29293958). Of note, this gene has also been implicated in autosomal recessive nonsyndromic hearing loss which has been
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