1. Genetic screening of LCA in Belgium: predominance of CEP290 and identification of potential modifier alleles in AHI1 of CEP290-related phenotypes
- Author
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Johan Vande Walle, Paul Coucke, Sophie Walraedt, Frauke Coppieters, Elfride De Baere, Hester Y. Kroes, Luis Nunes, Françoise Meire, Valerie Meersschaut, Nicole Van Regemorter, Thomy de Ravel, Ingele Casteels, Hilde Van Esch, Heidi Hoeben, Bart P. Leroy, Lieve Standaert, Sally Hooghe, Sarah De Jaegere, Aušra Matulevičienė, Center for Medical Genetics [Ghent], Ghent University Hospital, Department of Ophthalmology, Leuven University Hospitals, Ophthalmology, Hôpital Des Enfants Reine Fabiola, Centre de Génétique de Bruxelles, Université libre de Bruxelles (ULB), Centre for Human Genetics, University Hospital Leuven, Department of Human and Medical Genetics, Vilnius University [Vilnius], Eye Genetics Research Group, Westmead Hospital [Sydney]-Children's Medical Research Institute and Save Sight Institute-The University of Sydney, Department of Radiology, Revalidation Center Spermalie, Dpt. Medical Genetics - Head Collagen Lab, Department of Nephrology, Middelheim Hospital, Department of Biomedical Genetics, VU University Medical Center [Amsterdam], Department of Pediatrics, Clinical sciences, and Medical Genetics
- Subjects
Genotype-phenotype correlation ,Retinal Degeneration/genetics ,genetic structures ,DNA Mutational Analysis ,Leber Congenital Amaurosis ,Oligonucleotide Array Sequence Analysis/methods ,Cell Cycle Proteins ,Adaptor Proteins, Signal Transducing/genetics ,Bioinformatics ,0302 clinical medicine ,Neoplasm Proteins/genetics ,Belgium ,Leber Congenital Amaurosis/diagnosis ,Genotype ,Missense mutation ,Modifier ,Child ,Genetics (clinical) ,Oligonucleotide Array Sequence Analysis ,Genetics ,0303 health sciences ,CRB1 ,medicine.diagnostic_test ,LCA ,Retinal Degeneration ,Life Sciences ,Sciences bio-médicales et agricoles ,Middle Aged ,Neoplasm Proteins ,3. Good health ,Antigens, Neoplasm/genetics ,Phenotype ,Child, Preschool ,Proteins/genetics ,young adult ,GUCY2D ,CEP290 ,Adult ,Child, preschool ,Adolescent ,DNA Mutational Analysis/methods ,AHI1 ,HDE - GEN ,Mutation in Brief ,genotype-phenotype correlation ,Biology ,Joubert syndrome ,Young Adult ,03 medical and health sciences ,Antigens, Neoplasm ,Retinal Dystrophies ,Retinitis pigmentosa ,medicine ,Humans ,Genetic Testing ,Alleles ,Adaptor Proteins, Signal Transducing ,030304 developmental biology ,Genetic testing ,modifier ,Retinal Dystrophies/genetics ,Genetic heterogeneity ,Gene Expression Profiling ,Infant ,Proteins ,medicine.disease ,eye diseases ,Adaptor Proteins, Vesicular Transport ,Cytoskeletal Proteins ,030221 ophthalmology & optometry ,sense organs - Abstract
Leber Congenital Amaurosis (LCA), the most severe inherited retinal dystrophy, is genetically heterogeneous, with 14 genes accounting for 70% of patients. Here, 91 LCA probands underwent LCA chip analysis and subsequent sequencing of 6 genes (CEP290, CRB1, RPE65, GUCY2D, AIPL1and CRX), revealing mutations in 69% of the cohort, with major involvement of CEP290 (30%). In addition, 11 patients with early-onset retinal dystrophy (EORD) and 13 patients with Senior-Loken syndrome (SLS), LCA-Joubert syndrome (LCA-JS) or cerebello-oculo-renal syndrome (CORS) were included. Exhaustive re-inspection of the overall phenotypes in our LCA cohort revealed novel insights mainly regarding the CEP290-related phenotype. The AHI1 gene was screened as a candidate modifier gene in three patients with the same CEP290 genotype but different neurological involvement. Interestingly, a heterozygous novel AHI1 mutation, p.Asn811Lys, was found in the most severely affected patient. Moreover, AHI1 screening in five other patients with CEP290-related disease and neurological involvement revealed a second novel missense variant, p.His758Pro, in one LCA patient with mild mental retardation and autism. These two AHI1 mutations might thus represent neurological modifiers of CEP290-related disease., Journal Article, Research Support, Non-U.S. Gov't, FLWOA, SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2010
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