[en] 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 RPGRIP1 gene was identified, which was likely the deleterious and pathogenic mutation in the proband. Structurally, this mutation lost a retinitis pigmentosa GTPase regulator (RPGR)-interacting domain at the C-terminus which most likely impaired stability in the RPGRIP1 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 RPGRIP1 gene works as a pathogenic mutation that contributes to the progression of LCA.
Disciplines :
Ophthalmology
Author, co-author :
Imani, Saber; Key Laboratory of Epigenetics and Oncology, Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan, China ; Hunan Normal University Medical College, Changsha, Hunan, China ; Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
Cheng, Jingliang; Key Laboratory of Epigenetics and Oncology, Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan, China
Mobasher-Jannat, Abdolkarim; Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran ; Student Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran
Wei, Chunli; Key Laboratory of Epigenetics and Oncology, Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan, China
Fu, Shangyi; The Honors College, University of Houston, Houston, TX, USA ; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
Yang, Lisha; Key Laboratory of Epigenetics and Oncology, Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan, China
Jadidi, Khosrow; Department of Ophthalmology, Baqiyatallah University of Medical Sciences, Tehran, Iran
Khosravi, Mohammad Hossein ; Université de Liège - ULiège ; Student Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran
Mohazzab-Torabi, Saman; Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
Shasaltaneh, Marzieh Dehghan; Laboratory of Neuro-organic Chemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran ; Laboratory of Systems Biology and Bioinformatics (LBB), Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
Li, Yumei; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
Chen, Rui; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
Fu, Junjiang ; Key Laboratory of Epigenetics and Oncology, Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan, China ; Hunan Normal University Medical College, Changsha, Hunan, China
NSCF - National Natural Science Foundation of China [CN]
Funding text :
This work was supported in part by the National Natural Science Foundation of China (30371493, 81172049, 81672887), Science and Technology Innovation Team of Colleges and Universities of Sichuan Province in China (13TD0032), the Research Foundation of the Science and Technology Department of Sichuan Province in China (2015JY0038), the Research Foundation of the Education Department of Sichuan Province in China (17ZA0427, 17ZB0467), the Research Foundation of the Science and Technology Department of Liuzhou city in China (2013LZLY-J10, 2015-S-42(3/4)).
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