Sangermano, R;
Deitch, I;
Peter, VG;
Ba-Abbad, R;
Place, EM;
Zampaglione, E;
Wagner, NE;
... Bujakowska, KM; + view all
(2021)
Broadening INPP5E phenotypic spectrum: detection of rare variants in syndromic and non-syndromic IRD.
npj Genomic Medicine
, 6
, Article 53. 10.1038/s41525-021-00214-8.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Broadening INPP5E phenotypic spectrum: detection of rare variants in syndromic and non-syndromic IRD |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41525-021-00214-8 |
| Publisher version: | https://doi.org/10.1038/s41525-021-00214-8 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
| Keywords: | Disease genetics; Hereditary eye disease |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10131865 |
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