Broadening INPP5E phenotypic spectrum: detection of rare variants in syndromic and non-syndromic IRD.
Journal
NPJ genomic medicine
ISSN: 2056-7944
Titre abrégé: NPJ Genom Med
Pays: England
ID NLM: 101685193
Informations de publication
Date de publication:
29 Jun 2021
29 Jun 2021
Historique:
received:
18
12
2020
accepted:
21
05
2021
entrez:
30
6
2021
pubmed:
1
7
2021
medline:
1
7
2021
Statut:
epublish
Résumé
Pathogenic variants in INPP5E cause Joubert syndrome (JBTS), a ciliopathy with retinal involvement. However, despite sporadic cases in large cohort sequencing studies, a clear association with non-syndromic inherited retinal degenerations (IRDs) has not been made. We validate this association by reporting 16 non-syndromic IRD patients from ten families with bi-allelic mutations in INPP5E. Additional two patients showed early onset IRD with limited JBTS features. Detailed phenotypic description for all probands is presented. We report 14 rare INPP5E variants, 12 of which have not been reported in previous studies. We present tertiary protein modeling and analyze all INPP5E variants for deleteriousness and phenotypic correlation. We observe that the combined impact of INPP5E variants in JBTS and non-syndromic IRD patients does not reveal a clear genotype-phenotype correlation, suggesting the involvement of genetic modifiers. Our study cements the wide phenotypic spectrum of INPP5E disease, adding proof that sequence defects in this gene can lead to early-onset non-syndromic IRD.
Identifiants
pubmed: 34188062
doi: 10.1038/s41525-021-00214-8
pii: 10.1038/s41525-021-00214-8
pmc: PMC8242099
doi:
Types de publication
Journal Article
Langues
eng
Pagination
53Subventions
Organisme : NEI NIH HHS
ID : R01 EY026904
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD105351
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)
ID : R01EY012910
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : 31003A_176097
Organisme : Foundation Fighting Blindness (Foundation Fighting Blindness, Inc.)
ID : BR-GE-0214-0639-TECH
Organisme : NEI NIH HHS
ID : R01 EY012910
Pays : United States
Organisme : Foundation Fighting Blindness (Foundation Fighting Blindness, Inc.)
ID : EGI-GE-1218-0753-UCSD
Organisme : NEI NIH HHS
ID : P30 EY014104
Pays : United States
Organisme : Foundation Fighting Blindness (FFB)
ID : BR-GE-0214-0639-TECH
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