TY - JOUR
T1 - Broadening INPP5E phenotypic spectrum
T2 - detection of rare variants in syndromic and non-syndromic IRD
AU - Sangermano, Riccardo
AU - Deitch, Iris
AU - Peter, Virginie G.
AU - Ba-Abbad, Rola
AU - Place, Emily M.
AU - Zampaglione, Erin
AU - Wagner, Naomi E.
AU - Fulton, Anne B.
AU - Coutinho-Santos, Luisa
AU - Rosin, Boris
AU - Dunet, Vincent
AU - AlTalbishi, Ala’a
AU - Banin, Eyal
AU - Sousa, Ana Berta
AU - Neves, Mariana
AU - Larson, Anna
AU - Quinodoz, Mathieu
AU - Michaelides, Michel
AU - Ben-Yosef, Tamar
AU - Pierce, Eric A.
AU - Rivolta, Carlo
AU - Webster, Andrew R.
AU - Arno, Gavin
AU - Sharon, Dror
AU - Huckfeldt, Rachel M.
AU - Bujakowska, Kinga M.
N1 - Publisher Copyright: © 2021, The Author(s).
PY - 2021/6/29
Y1 - 2021/6/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85109035764&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41525-021-00214-8
DO - https://doi.org/10.1038/s41525-021-00214-8
M3 - مقالة
C2 - 34188062
SN - 2056-7944
VL - 6
JO - npj Genomic Medicine
JF - npj Genomic Medicine
IS - 1
M1 - 53
ER -