Novel loss-of-function variants in CDC14A are associated with recessive sensorineural hearing loss in Iranian and Pakistani patients
Please always quote using this URN: urn:nbn:de:bvb:20-opus-285142
- CDC14A encodes the Cell Division Cycle 14A protein and has been associated with autosomal recessive non-syndromic hearing loss (DFNB32), as well as hearing impairment and infertile male syndrome (HIIMS) since 2016. To date, only nine variants have been associated in patients whose initial symptoms included moderate-to-profound hearing impairment. Exome analysis of Iranian and Pakistani probands who both showed bilateral, sensorineural hearing loss revealed a novel splice site variant (c.1421+2T>C, p.?) that disrupts the splice donor site and aCDC14A encodes the Cell Division Cycle 14A protein and has been associated with autosomal recessive non-syndromic hearing loss (DFNB32), as well as hearing impairment and infertile male syndrome (HIIMS) since 2016. To date, only nine variants have been associated in patients whose initial symptoms included moderate-to-profound hearing impairment. Exome analysis of Iranian and Pakistani probands who both showed bilateral, sensorineural hearing loss revealed a novel splice site variant (c.1421+2T>C, p.?) that disrupts the splice donor site and a novel frameshift variant (c.1041dup, p.Ser348Glnfs*2) in the gene CDC14A, respectively. To evaluate the pathogenicity of both loss-of-function variants, we analyzed the effects of both variants on the RNA-level. The splice variant was characterized using a minigene assay. Altered expression levels due to the c.1041dup variant were assessed using RT-qPCR. In summary, cDNA analysis confirmed that the c.1421+2T>C variant activates a cryptic splice site, resulting in a truncated transcript (c.1414_1421del, p.Val472Leufs*20) and the c.1041dup variant results in a defective transcript that is likely degraded by nonsense-mediated mRNA decay. The present study functionally characterizes two variants and provides further confirmatory evidence that CDC14A is associated with a rare form of hereditary hearing loss.…
Author: | Julia Doll, Susanne Kolb, Linda Schnapp, Aboulfazl Rad, Franz Rüschendorf, Imran Khan, Abolfazl Adli, Atefeh Hasanzadeh, Daniel Liedtke, Sabine Knaup, Michaela AH Hofrichter, Tobias Müller, Marcus Dittrich, Il-Keun Kong, Hyung-Goo Kim, Thomas Haaf, Barbara Vona |
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URN: | urn:nbn:de:bvb:20-opus-285142 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Institut für Humangenetik |
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften | |
Language: | English |
Parent Title (English): | International Journal of Molecular Sciences |
ISSN: | 1422-0067 |
Year of Completion: | 2020 |
Volume: | 21 |
Issue: | 1 |
Article Number: | 311 |
Source: | International Journal of Molecular Sciences (2020) 21:1, 311. https://doi.org/10.3390/ijms21010311 |
DOI: | https://doi.org/10.3390/ijms21010311 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | CDC14A; DFNB32; autosomal recessive hearing loss; exome sequencing; frameshift; non-sense mediated mRNA decay; splicing |
Release Date: | 2023/06/12 |
Date of first Publication: | 2020/01/02 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |