Genetic screening of LCA in Belgium: predominance of CEP290 and identification of potential modifier alleles in AHI1 of CEP290 -related phenotypes
International audience ; Leber Congenital Amaurosis (LCA), the most severe inherited retinal dystrophies, 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 , AIPL1 and 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 incl... Mehr ...
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Dokumenttyp: | Artikel |
Erscheinungsdatum: | 2010 |
Verlag/Hrsg.: |
HAL CCSD
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Schlagwörter: | Life Sciences |
Sprache: | Englisch |
Permalink: | https://search.fid-benelux.de/Record/base-26608740 |
Datenquelle: | BASE; Originalkatalog |
Powered By: | BASE |
Link(s) : | https://hal.archives-ouvertes.fr/hal-00613751 |
International audience ; Leber Congenital Amaurosis (LCA), the most severe inherited retinal dystrophies, 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 , AIPL1 and 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.