Novel nonsense and splice site mutations in CRB1 gene in two Japanese patients with early-onset retinal dystrophy
To report novel mutations in the CRB1 gene in two patients with early-onset retinal dystrophy (EORD) and the longitudinal clinical course of EORD.
Patients and methods
The patients were two unrelated Japanese children. Standard ophthalmic examinations including perimetry, electroretinography, and optical coherence tomography were performed on both patients. Whole exomes of the patients and their nonsymptomatic parents were analyzed using a next-generation sequence (NGS) technique.
Patient 1 was noted to have esotropia and hyperopia at age 3. His decimal best-corrected visual acuity (BCVA) was 0.6 OD and 0.3 OS at age 6 with de-pigmentation of the retinal pigment epithelium (RPE). At age 19, his central vision was still preserved; however, numerous pigment granules were present in the retina. NGS analysis revealed a p.R632X nonsense and c.652 + 1_652 + 4delGTAA splice site mutations in the CRB1 gene. Patient 2 was noted to have hyperopia at age 3. His decimal BCVA at age 6 was 0.3 OD and 0.4 OS with de-pigmented RPE. The degree of retinal pigmentation was increased but his BCVA was good until the age of 14 years. NGS analysis revealed c.652 + 1_652 + 4delGTAA and c.652 + 1_652 + 2insT splice site mutations in the CRB1 gene.
The phenotypes of these novel mutations for EORD are typical of CRB1-associated EORD (LCA8). They were slowly progressive until the second decade of life.
KeywordsLeber congenital amaurosis Early-onset retinal dystrophy CRB1 Optical coherence tomography Electroretinography Visual fields Japanese
This research was supported by the research Grants to T.I., K.T., Y.S., and K.K. from the Ministry of Health, Labour and Welfare, Japan (13803661, 23164001, and 82259921), to S.K. and K.K. from Japan Society for the Promotion of Science, Japan (23592597), and to M.F. from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) for RIKEN Center for Life Science Technologies.
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