TY  - JOUR
A1  - Doll, Julia
A1  - Kolb, Susanne
A1  - Schnapp, Linda
A1  - Rad, Aboulfazl
A1  - Rüschendorf, Franz
A1  - Khan, Imran
A1  - Adli, Abolfazl
A1  - Hasanzadeh, Atefeh
A1  - Liedtke, Daniel
A1  - Knaup, Sabine
A1  - Hofrichter, Michaela AH
A1  - Müller, Tobias
A1  - Dittrich, Marcus
A1  - Kong, Il-Keun
A1  - Kim, Hyung-Goo
A1  - Haaf, Thomas
A1  - Vona, Barbara
T1  - Novel loss-of-function variants in CDC14A are associated with recessive sensorineural hearing loss in Iranian and Pakistani patients
JF  - International Journal of Molecular Sciences
N2  - 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 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.
KW  - CDC14A
KW  - DFNB32
KW  - autosomal recessive hearing loss
KW  - exome sequencing
KW  - splicing
KW  - frameshift
KW  - non-sense mediated mRNA decay
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285142
SN  - 1422-0067
VL  - 21
IS  - 1
ER  -