PhenoModifier-Variant Detail

Variant "PSEN1:c.709T>C(p.Phe237Leu)"

Search result: 1 record

Variant information

Gene:

PSEN1

Variant:

PSEN1:c.709T>C(p.Phe237Leu)

Genomic location:

chr14:73659512(hg19)

HGVS:

SO Term	RefSeq
protein_coding	NM_000021.3:c.709T>C(p.Phe237Leu)
protein_coding	NM_007318.2:c.697T>C(p.Phe233Leu)

dbSNP ID:

rs63750858

GWAS trait:

no data

Modifier statisitcs

Record:

1

Disorder:

1

Reference:

1

Effect type:

Penetrance(1)

Modifier effect:

Altered incidence(1)

Detail：

Target disease:

Alzheimer's Disease (DOID_10652)

Effect type:

Penetrance

Modifier effect:

Altered incidence

Evidence:

From review article

Effect:

A protective factor in some individuals and raise the prospect that modifier genes may underlie this phenotypic heterogeneity.

Reference:

PMID17995932

Title:

Variable phenotype of Alzheimer's disease with spastic paraparesis.

Species studied:

Human

Abstract:

Pedigrees with familial Alzheimer's disease (AD) show considerable phenotypic variability. Spastic paraparesis (SP), or progressive spasticity of the lower limbs is frequently hereditary and exists either as uncomplicated (paraparesis alone) or complicated (paraparesis and other neurological features) disease subtypes. In some AD families, with presenilin-1 (PSEN1) mutations, affected individuals also have SP. These PSEN1 AD pedigrees frequently have a distinctive and variant neuropathology, namely large, non-cored plaques without neuritic dystrophy called cotton wool plaques (CWP). The PSEN1 AD mutations giving rise to CWP produce unusually high levels of the amyloid beta peptide (Abeta) ending at position 42 or 43, and the main component of CWP is amino-terminally truncated forms of amyloid beta peptide starting after the alternative beta-secretase cleavage site at position 11. This suggests a molecular basis for the formation of CWP and an association with both SP and AD. The SP phenotype in some PSEN1 AD pedigrees also appears to be associated with a delayed onset of dementia compared with affected individuals who present with dementia only, suggesting the existence of a protective factor in some individuals with SP. Variations in neuropathology and neurological symptoms in PSEN1 AD raise the prospect that modifier genes may underlie this phenotypic heterogeneity.