Open AccessIdentification of a novel RPGRIP 1 mutation in an Iranian family with leber congenital amaurosis by exome sequencing
Author(s) -
Imani Saber,
Cheng Jingliang,
MobasherJannat Abdolkarim,
Wei Chunli,
Fu Shangyi,
Yang Lisha,
Jadidi Khosrow,
Khosravi Mohammad Hossein,
MohazzabTorabi Saman,
Shasaltaneh Marzieh Dehghan,
Li Yumei,
Chen Rui,
Fu Junjiang
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13454
Subject(s) - proband , sanger sequencing , exome sequencing , retinitis pigmentosa , genetics , mutation , biology , fundus photography , medicine , gene , retinal , ophthalmology , fluorescein angiography
Leber congenital amaurosis ( LCA ) is a heterogeneous, early‐onset inherited retinal dystrophy, which is associated with severe visual impairment. We aimed to determine the disease‐causing variants in Iranian LCA and evaluate the clinical implications. Clinically, a possible LCA disease was found through diagnostic imaging, such as fundus photography, autofluorescence and optical coherence tomography. All affected patients showed typical eye symptoms associated with LCA including narrow arterioles, blindness, pigmentary changes and nystagmus. Target exome sequencing was performed to analyse the proband DNA . A homozygous novel c. 2889delT (p.P963 fs) mutation in the RPGRIP 1 gene was identified, which was likely the deleterious and pathogenic mutation in the proband. Structurally, this mutation lost a retinitis pigmentosa GTP ase regulator ( RPGR )‐interacting domain at the C‐terminus which most likely impaired stability in the RPGRIP 1 with the distribution of polarised proteins in the cilium connecting process. Sanger sequencing showed complete co‐segregation in this pedigree. This study provides compelling evidence that the c. 2889delT (p.P963 fs) mutation in the RPGRIP 1 gene works as a pathogenic mutation that contributes to the progression of LCA .