genetics
human genetics
molecular biology
mutation, missense
phenotype
Journal
Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R
Informations de publication
Date de publication:
30 Jun 2023
30 Jun 2023
Historique:
received:
08
03
2023
accepted:
09
06
2023
medline:
3
7
2023
pubmed:
3
7
2023
entrez:
3
7
2023
Statut:
aheadofprint
Résumé
Otosclerosis is a common cause of adult-onset progressive hearing loss, affecting 0.3%-0.4% of the population. It results from dysregulation of bone homeostasis in the otic capsule, most commonly leading to fixation of the stapes bone, impairing sound conduction through the middle ear. Otosclerosis has a well-known genetic predisposition including familial cases with apparent autosomal dominant mode of inheritance. While linkage analysis and genome-wide association studies suggested an association with several genomic loci and with genes encoding structural proteins involved in bone formation or metabolism, the molecular genetic pathophysiology of human otosclerosis is yet mostly unknown. Whole-exome sequencing, linkage analysis, generation of CRISPR mutant mice, hearing tests and micro-CT. Through genetic studies of kindred with seven individuals affected by apparent autosomal dominant otosclerosis, we identified a disease-causing variant in We demonstrate that otosclerosis can be caused by a variant in
Sections du résumé
BACKGROUND
BACKGROUND
Otosclerosis is a common cause of adult-onset progressive hearing loss, affecting 0.3%-0.4% of the population. It results from dysregulation of bone homeostasis in the otic capsule, most commonly leading to fixation of the stapes bone, impairing sound conduction through the middle ear. Otosclerosis has a well-known genetic predisposition including familial cases with apparent autosomal dominant mode of inheritance. While linkage analysis and genome-wide association studies suggested an association with several genomic loci and with genes encoding structural proteins involved in bone formation or metabolism, the molecular genetic pathophysiology of human otosclerosis is yet mostly unknown.
METHODS
METHODS
Whole-exome sequencing, linkage analysis, generation of CRISPR mutant mice, hearing tests and micro-CT.
RESULTS
RESULTS
Through genetic studies of kindred with seven individuals affected by apparent autosomal dominant otosclerosis, we identified a disease-causing variant in
CONCLUSION
CONCLUSIONS
We demonstrate that otosclerosis can be caused by a variant in
Identifiants
pubmed: 37399313
pii: jmg-2023-109264
doi: 10.1136/jmg-2023-109264
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDCD NIH HHS
ID : R01 DC011835
Pays : United States
Informations de copyright
© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.