Parkinson Disease and Complex Parkinsonism

Gene: EIF4G1

Red List (low evidence)

Monoallelic mutations have been described in PD, but the pathogenicity of EIF4G1 mutations is debated. The R1205H variant was reported in a family with 10 affected members and one sporadic Irish patient (Chartier-Harlin et al., 2011) (McCarthy, 2014). The A502V variant was found in two other sporadic PD patients (Chartier-Harlin et al., 2011). Subsequently number of studies identified R1205H in both patients and controls (Nuytemans et al., 2013; Dhungel et al., 2015; Nichols et al., 2015), suggesting that it is a benign poymorphism.

Created: 14 Dec 2016, 5:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

PMID:23462481 lists EIF4G1 as one of the 7 Mendelian genes, but there isn't conclusive evidence for a pathogenic role based on PMID:26022768 and 25368108.

Created: 10 Nov 2016, 4:26 p.m.

Comment on list classification: Two founder mutations reported so far. PMID: 25368108 screened 2051 sporadic PD patients for the two reported variants, and sequenced the gene in 95 familial PD patients with autosomal-dominant inheritance. They state that their data do not support the EIF4G1 gene as a high-risk PD locus, neither for the familial nor the sporadic condition. And concude that caution should be exercised when interpreting EIF4G1 genotyping results in isolated patients and PD families, and diagnostic testing of EIF4G1 should not be recommended in clinical settings.

Created: 3 Nov 2016, 11:19 a.m.