Title: Genetic screening of LCA in Belgium: predominance of CEP290 and identification of potential modifier alleles in AHI1 of CEP290-related phenotypes
Authors: Coppieters, Frauke
Casteels, Ingele
Meire, Françoise
De Jaegere, Sarah
Hooghe, Sally
van Regemorter, Nicole
Van Esch, Hilde
Matulevičienė, Aušra
Nunes, Luis
Meersschaut, Valérie
Walraedt, Sophie
Standaert, Lieve
Coucke, Paul
Hoeben, Heidi
Kroes, Hester Y
Vande Walle, Johan
de Ravel de l'Argentière, Thomy
Leroy, Bart P
De Baere, Elfride # ×
Issue Date: Oct-2010
Publisher: John Wiley & Sons, Inc.
Series Title: Human Mutation vol:31 issue:10 pages:E1709-E1766
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. (c) 2010 Wiley-Liss, Inc.
ISSN: 1059-7794
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Research Group Ophthalmology
Clinical Genetics
× corresponding author
# (joint) last author

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