Parkinson's disease due to the R1441G mutation in Dardarin: a founder effect in the Basques

Area of Science:

• Genetics
• Neurology
• Human Ancestry

Background:

• Mutations in the Leucine-Rich Repeat Kinase 2 (LRRK2) gene are associated with familial Parkinson's disease (PD).
• The R1441G LRRK2 mutation has been identified in both familial and sporadic Parkinson's disease cases, particularly in individuals of Basque descent.

Purpose of the Study:

• To investigate the prevalence and clinical presentation of the R1441G LRRK2 mutation in a Basque population.
• To determine if the R1441G mutation in Parkinson's disease patients of Basque descent is linked to a common ancestor.

Main Methods:

• Allele-specific polymerase chain reaction (PCR) was used to detect the R1441G mutation.
• Single nucleotide polymorphisms (SNPs) near the mutation were analyzed via direct sequencing.
• Subjects were classified by Basque and non-Basque ancestry.

Main Results:

• The R1441G mutation was found in 22 members of original Basque families and an additional 17 individuals, suggesting a common ancestral link.
• Parkinson's disease in R1441G mutation carriers was clinically indistinguishable from that in non-carriers.
• The R1441G mutation was present in 16.4% of familial PD and 4.0% of sporadic PD cases within the studied Basque population.

Conclusions:

• The R1441G LRRK2 mutation is a significant genetic factor in Parkinson's disease within the Basque population.
• The R1441G mutation leads to a form of Parkinson's disease clinically equivalent to idiopathic PD.
• The mutation's prevalence suggests a founder effect or genetic drift within this specific ancestral group.