ADAMTS1, MPDZ, MVD, and SEZ6: candidate genes for autosomal recessive nonsyndromic hearing impairment.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
19
02
2021
accepted:
21
05
2021
revised:
12
05
2021
pubmed:
18
6
2021
medline:
24
3
2022
entrez:
17
6
2021
Statut:
ppublish
Résumé
Hearing impairment (HI) is a common disorder of sensorineural function with a highly heterogeneous genetic background. Although substantial progress has been made in the understanding of the genetic etiology of hereditary HI, many genes implicated in HI remain undiscovered. Via exome and Sanger sequencing of DNA samples obtained from consanguineous Pakistani families that segregate profound prelingual sensorineural HI, we identified rare homozygous missense variants in four genes (ADAMTS1, MPDZ, MVD, and SEZ6) that are likely the underlying cause of HI. Linkage analysis provided statistical evidence that these variants are associated with autosomal recessive nonsyndromic HI. In silico analysis of the mutant proteins encoded by these genes predicted structural, conformational or interaction changes. RNAseq data analysis revealed expression of these genes in the sensory epithelium of the mouse inner ear during embryonic, postnatal, and adult stages. Immunohistochemistry of the mouse cochlear tissue, further confirmed the expression of ADAMTS1, SEZ6, and MPDZ in the neurosensory hair cells of the organ of Corti, while MVD expression was more prominent in the spiral ganglion cells. Overall, supported by in silico mutant protein analysis, animal models, linkage analysis, and spatiotemporal expression profiling in the mouse inner ear, we propose four new candidate genes for HI and expand our understanding of the etiology of HI.
Identifiants
pubmed: 34135477
doi: 10.1038/s41431-021-00913-x
pii: 10.1038/s41431-021-00913-x
pmc: PMC8738740
doi:
Substances chimiques
MPDZ protein, human
0
Membrane Proteins
0
SEZ6L protein, human
0
ADAMTS1 Protein
EC 3.4.24.-
ADAMTS1 protein, human
EC 3.4.24.-
Carboxy-Lyases
EC 4.1.1.-
pyrophosphomevalonate decarboxylase
EC 4.1.1.33
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
22-33Subventions
Organisme : NIDCD NIH HHS
ID : R01 DC011651
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC003594
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG006493
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG008956
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021. The Author(s).
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