PhenoModifier-Variant Detail

Variant "AHI1:c.2433T>G(p.Asn811Lys)"

Search result: 1 record

Variant information

Gene:

AHI1

Variant:

AHI1:c.2433T>G(p.Asn811Lys)

Genomic location:

chr6:135751079(hg19)

HGVS:

SO Term	RefSeq
protein_coding	NM_001134830.1:c.2433T>G(p.Asn811Lys)
protein_coding	NM_001134831.1:c.2433T>G(p.Asn811Lys)
protein_coding	NM_017651.4:c.2433T>G(p.Asn811Lys)
protein_coding	NM_001134832.1:c.2433T>G(p.Asn811Lys)

dbSNP ID:

rs750173862

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.