Variant "AHI1:p.His758Pro"
Search result: 1 record
Variant information
Gene:
AHI1 
Variant:
AHI1:p.His758Pro 
dbSNP ID:
no data 
GWAS trait:
no data 
Modifier statisitcs
Record:
1 
Disorder:
1 
Reference:
1 
Effect type:
Expressivity(1)  
Modifier effect:
Altered severity(1)  
Detail：
  • Target disease:
    Leber Congenital Amaurosis (DOID_14791)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered severity 
    Evidence:
    Assessment of genotype–phenotype associations 
    Effect:
    These two AHI1 mutations might thus represent neurological modifiers of CEP290-related disease
    Reference:
    PMID20683928
    Title:
    Genetic screening of LCA in Belgium: predominance of CEP290 and identification of potential modifier alleles in AHI1 of CEP290-related phenotypes.
    Species studied:
    Human
    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.