Novel genetic causes for cerebral visual impairment

Cerebral visual impairment (CVI) is a major cause of low vision in children due to impairment in projection and/or interpretation of the visual input in the brain. Although acquired causes for CVI are well known, genetic causes underlying CVI are largely unidentified. DNAs of 25 patients with CVI an...

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Bibliographic Details
Published in:European journal of human genetics : EJHG 2016-05, Vol.24 (5), p.660-665
Main Authors: Bosch, Daniëlle G M, Boonstra, F Nienke, de Leeuw, Nicole, Pfundt, Rolph, Nillesen, Willy M, de Ligt, Joep, Gilissen, Christian, Jhangiani, Shalini, Lupski, James R, Cremers, Frans P M, de Vries, Bert B A
Format: Article
Language:English
Subjects:
Adolescent
Blindness
Blindness, Cortical - diagnosis
Blindness, Cortical - genetics
Child
Child, Preschool
Children
Classification
Data processing
Epilepsy
Families & family life
Female
Genes
Genetic diversity
Genetic Loci
Genetic screening
Genetics
Genomes
Heredity
Humans
Intellectual disabilities
KCNQ3 protein
Male
Mutation
Polymorphism, Single Nucleotide
Potassium channels (voltage-gated)
Visual impairment
Young Adult
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Summary:Cerebral visual impairment (CVI) is a major cause of low vision in children due to impairment in projection and/or interpretation of the visual input in the brain. Although acquired causes for CVI are well known, genetic causes underlying CVI are largely unidentified. DNAs of 25 patients with CVI and intellectual disability, but without acquired (eg, perinatal) damage, were investigated by whole-exome sequencing. The data were analyzed for de novo, autosomal-recessive, and X-linked variants, and subsequently classified into known, candidate, or unlikely to be associated with CVI. This classification was based on the Online Mendelian Inheritance in Man database, literature reports, variant characteristics, and functional relevance of the gene. After classification, variants in four genes known to be associated with CVI (AHDC1, NGLY1, NR2F1, PGAP1) in 5 patients (20%) were identified, establishing a conclusive genetic diagnosis for CVI. In addition, in 11 patients (44%) with CVI, variants in one or more candidate genes were identified (ACP6, AMOT, ARHGEF10L, ATP6V1A, DCAF6, DLG4, GABRB2, GRIN1, GRIN2B, KCNQ3, KCTD19, RERE, SLC1A1, SLC25A16, SLC35A2, SOX5, UFSP2, UHMK1, ZFP30). Our findings show that diverse genetic causes underlie CVI, some of which will provide insight into the biology underlying this disease process.
ISSN:1018-4813
1476-5438
DOI:10.1038/ejhg.2015.186