Founder mutation for Huntington disease in Caucasus Jews

Area of Science:

• Genetics
• Neurology
• Population Studies

Background:

• Huntington disease (HD) is an autosomal dominant neurodegenerative disorder.
• Diagnosis and onset age are linked to CAG repeat expansion in the HTT gene.
• HD prevalence is established in Europeans but not well-studied in Israeli populations.

Purpose of the Study:

• To investigate the prevalence and genetic origins of Huntington disease (HD) in the Israeli population.
• To determine if a founder mutation exists within specific Jewish subgroups.

Main Methods:

• Haplotype analysis of ten HD probands diagnosed between 2006-2011.
• Focus on nine Caucasus Jewish (CJ) and one Ashkenazi Jewish proband.
• Calculation of mutation coalescence age.

Main Results:

• Eight of nine CJ probands shared a common haplotype (A1 haplogroup), suggesting a founder effect.
• The mutation's coalescence age was estimated between 80-150 years.
• CJ constitute 90% of local HD patients and 27% of all Israeli HD cases, despite being 1.4% of the population.

Conclusions:

• HD prevalence is significantly higher among Caucasus Jews (CJ) in Israel compared to the general population.
• Findings support a recent founder mutation for HD within the CJ community.
• Increased clinical suspicion for HD is recommended in CJ individuals presenting with subtle symptoms.