Tissue-specific genotype-phenotype correlations among USH2A-related disorders in the RUSH2A study.
USH2A
Usher syndrome
genotype
hearing loss
photoreceptor degeneration
retinitis pigmentosa
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
revised:
24
02
2022
received:
24
11
2021
accepted:
04
03
2022
pubmed:
11
3
2022
medline:
21
4
2022
entrez:
10
3
2022
Statut:
ppublish
Résumé
We assessed genotype-phenotype correlations among the visual, auditory, and olfactory phenotypes of 127 participants with Usher syndrome (USH2) (n =80) or nonsyndromic autosomal recessive retinitis pigmentosa (ARRP) (n = 47) due to USH2A variants, using clinical data and molecular diagnostics from the Rate of Progression in USH2A Related Retinal Degeneration (RUSH2A) study. USH2A truncating alleles were associated with USH2 and had a dose-dependent effect on hearing loss severity with no effect on visual loss severity within the USH2 subgroup. A group of missense alleles in an interfibronectin domain appeared to be hypomorphic in ARRP. These alleles were associated with later age of onset, larger visual field area, better sensitivity thresholds, and better electroretinographic responses. No effect of genotype on the severity of olfactory deficits was observed. This study unveils a unique, tissue-specific USH2A allelic hierarchy with important prognostic implications for patient counseling and treatment trial endpoints. These findings may inform clinical care or research approaches in others with allelic disorders or pleiotropic phenotypes.
Identifiants
pubmed: 35266249
doi: 10.1002/humu.24365
pmc: PMC9018588
mid: NIHMS1787078
doi:
Substances chimiques
Extracellular Matrix Proteins
0
USH2A protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
613-624Subventions
Organisme : NIDCD NIH HHS
ID : R01 DC000064
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 DC000064
Pays : United States
Organisme : Foundation Fighting Blindness
ID : RUSH2A - CONSORTIUM - 2016
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA EY000565
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY002162
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA EY000564
Pays : United States
Informations de copyright
© 2022 Wiley Periodicals LLC.
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