Journal article
When transcripts matter: delineating between non-syndromic hearing loss DFNB32 and hearing impairment infertile male syndrome (HIIMS)
Journal of human genetics, Vol.65(7), pp.609-617
07/01/2020
DOI: 10.1038/s10038-020-0740-z
PMCID: PMC7651993
PMID: 32231217
Abstract
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.
Details
- Title: Subtitle
- When transcripts matter: delineating between non-syndromic hearing loss DFNB32 and hearing impairment infertile male syndrome (HIIMS)
- Creators
- Marzieh Mohseni - University of Social Welfare and Rehabilitation SciencesMojdeh Akbari - University of Social Welfare and Rehabilitation SciencesKevin T Booth - Harvard Medical SchoolMojgan Babanejad - University of Social Welfare and Rehabilitation SciencesHela Azaiez - University of IowaFariba Ardalani - University of Social Welfare and Rehabilitation SciencesSanaz Arzhangi - University of Social Welfare and Rehabilitation SciencesKhadijeh Jalalvand - University of Social Welfare and Rehabilitation SciencesNooshin Nikzat - University of Social Welfare and Rehabilitation SciencesFatemeh Ghodratpour - University of Social Welfare and Rehabilitation SciencesPayman Jamali - Counseling CenterOmid Ali Adeli - Department of Pathology, Medical University, Kordestan, Iran.Haleh Habibi - Hamedan University of Medical SciencesKimia Kahrizi - University of Social Welfare and Rehabilitation SciencesHossein Najmabadi - University of Social Welfare and Rehabilitation Sciences
- Resource Type
- Journal article
- Publication Details
- Journal of human genetics, Vol.65(7), pp.609-617
- DOI
- 10.1038/s10038-020-0740-z
- PMID
- 32231217
- PMCID
- PMC7651993
- NLM abbreviation
- J Hum Genet
- ISSN
- 1434-5161
- eISSN
- 1435-232X
- Grant note
- 96011200 / Iran National Science Foundation (INSF) T32 GM007748 / NIGMS NIH HHS
- Language
- English
- Date published
- 07/01/2020
- Academic Unit
- Otolaryngology
- Record Identifier
- 9984383298602771
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