Broadening INPP5E phenotypic spectrum: detection of rare variants in syndromic and non-syndromic IRD.

Détails

Ressource 1Télécharger: s41525-021-00214-8.pdf (4140.16 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_03A6B6C61DF5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Broadening INPP5E phenotypic spectrum: detection of rare variants in syndromic and non-syndromic IRD.
Périodique
NPJ genomic medicine
Auteur⸱e⸱s
Sangermano R., Deitch I., Peter V.G., Ba-Abbad R., Place E.M., Zampaglione E., Wagner N.E., Fulton A.B., Coutinho-Santos L., Rosin B., Dunet V., AlTalbishi A., Banin E., Sousa A.B., Neves M., Larson A., Quinodoz M., Michaelides M., Ben-Yosef T., Pierce E.A., Rivolta C., Webster A.R., Arno G., Sharon D., Huckfeldt R.M., Bujakowska K.M.
ISSN
2056-7944 (Electronic)
ISSN-L
2056-7944
Statut éditorial
Publié
Date de publication
29/06/2021
Peer-reviewed
Oui
Volume
6
Numéro
1
Pages
53
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: 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.
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/07/2021 11:19
Dernière modification de la notice
18/10/2023 7:12
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