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Elise Heon, Shuning Li, Erika Tavares, Heather Macdonald, Ajoy Vincent; SRD5A3: a gene for complex LCA and early onset retinal dystrophy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3134.
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© 2017 Association for Research in Vision and Ophthalmology.
To identify the genetic basis of LCA/early onset retinal dystrophy(EORD) in a cohort of patients for whom all known genes have been excluded through clinically available testing of the known genes.
All 10 cases have been extensively phenotyped; comprehensive eye examination, full-field electroretinography (ERG), retinal imaging and documentation of any systemic features or positive family findings were available. Whole exome sequencing was performed on 10 individuals with the clinical diagnosis of LCA/EORD with no mutations identified on clinical LCA genetic testing. We used the Illumina Hi-Seq 2000 platform after target enrichment of 6.5µg of genomic DNA with the Agilent SureSelectHuman All Exon 50Mb Capture kit.
Two unrelated individuals (18 months and 18 years) were identified with the same homozygous mutation (p.Trp19Ter) in SRD5A3. Both individuals had some developmental delay. normal brain MRI and one proband had microcephaly. They were otherwise healthy. The ERG was severely attenuated, nystagmus was present in the first six months of life and associated with significant vision loss in both probands.
Mutations in SRD5A3 (5-alpha steroid reductase) cause congenital disorder of glycosylation type 1q (CGD1q) usually characterized by developmental delay, brain and ocular developmental anomalies. SRD5A3 is necessary for the reduction of polyprenol to dolichol, the lipid anchor for N-glycosylation in the endoplasmic reticulum. This mutation could affect the glycosylation of rhodopsin which is required for its incorporation in the photoreceptor. Non-glycosylated rhodopsin is associated with retinal degeneration. The CGD1q phenotypes reported here are novel and broaden the phenotypic spectrum variability associated with mutations in SRD5A3. Glycosylation defects may be an under-recognized cause of retinal degeneration.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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