title: Founder mutation for Huntington disease in Caucasus Jews.
abstract: Huntington disease (HD), an autosomal dominant disorder involving HTT, is characterized by chorea, psychiatric illness and cognitive decline. Diagnosis and age of onset depend on the degree of expansion of the trinucleotide CAG repeat within the gene. The prevalence of HD is known for Europeans but has not been studied in the Israeli population. Between 2006 and 2011 we diagnosed in our adult genetics clinic ten HD probands, nine of whom were Caucasus Jews (CJ) (Azerbaijani), and one Ashkenazi Jewish. We performed haplotype analysis to look for evidence of a founder mutation, and found that of the nine CJ, eight shared the same haplotype that was compatible with the A1 haplogroup. We calculated the coalescence age of the mutation to be between 80 and 150 years. Ninety percent of our HD patients are CJ, as are 27% of the HD patients in Israel, although the CJ comprise only 1.4% of the Israeli population. Our findings suggest a higher prevalence of HD among CJ compared to the general Israeli population and are consistent with a recent founder mutation. We recommend a higher degree of suspicion for HD in CJ with subtle clinical findings.
authors.affiliation: The Raphael Recanati Genetic Institute, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Melamed
authors.forename: D M
authors.initials: DM
authors.lastname: Behar
authors.forename: C
authors.initials: C
authors.lastname: Bram
authors.forename: N
authors.initials: N
authors.lastname: Magal
authors.forename: E
authors.initials: E
authors.lastname: Pras
authors.forename: H
authors.initials: H
authors.lastname: Reznik-Wolf
authors.forename: Z U
authors.initials: ZU
authors.lastname: Borochowitz
authors.forename: B
authors.initials: B
authors.lastname: Davidov
authors.forename: R
authors.initials: R
authors.lastname: Mor-Cohen
authors.forename: H N
authors.initials: HN
authors.lastname: Baris
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D006580:Genetic Carrier Screening; D006239:Haplotypes; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics*; D007557:Israel; D007585:Jews / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D018911:Trinucleotide Repeats; D044465:White People
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins
keywords: Caucasus Jews; Huntington disease; founder mutation; haplotype