@article {1598069, title = {Broadening INPP5E phenotypic spectrum: detection of rare variants in syndromic and non-syndromic IRD}, journal = {NPJ Genom Med}, volume = {6}, number = {1}, year = {2021}, month = {2021 Jun 29}, pages = {53}, 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.}, issn = {2056-7944}, doi = {10.1038/s41525-021-00214-8}, author = {Sangermano, Riccardo and Deitch, Iris and Peter, Virginie G and Ba-Abbad, Rola and Place, Emily M and Zampaglione, Erin and Wagner, Naomi E and Fulton, Anne B and Coutinho-Santos, Luisa and Rosin, Boris and Dunet, Vincent and AlTalbishi, Ala{\textquoteright}a and Banin, Eyal and Sousa, Ana Berta and Neves, Mariana and Larson, Anna and Quinodoz, Mathieu and Michaelides, Michel and Ben-Yosef, Tamar and Pierce, Eric A and Rivolta, Carlo and Webster, Andrew R and Arno, Gavin and Sharon, Dror and Huckfeldt, Rachel M and Bujakowska, Kinga M} }