Huntington disease-like 2 (HDL2) in Venezuela: frequency and ethnic origin.

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Huntington disease (HD ) phenotypes without a HTT mutation are known as HD-like (HDL ) syndromes and are caused by mutations in other loci . HDL 2 , almost indistinguishable from HD , is due to expansions in the Junctophilin 3 locus (JPH 3 ) with a worldwide Sub-Saharan ethnic origin . Sixteen independent patients with involuntary movements , psychiatric disturbances and ataxia not having a HTT mutation were searched for loci PRNP (prion protein , HDL 1 ), JPH 3 (HDL 2 ), ATN 1 (dentatorubral-pallidoluysian atrophy ), ATX 2 (spinocerebellar ataxia 2 ) ATXN 3 (spinocerebellar ataxia 3 ), and TBP (spinocerebellar ataxia 17 =HDL 4 ). Markers Duffy , Kell , Diego , D 9 S 1120 , plus six JPH 3 intragenic single -nucleotide polymorphisms were tested to ascertain ethnic origin . Four unrelated choreic patients had an expanded allele at JPH 3 . Three of them carried the African marker Duffy null . All four families carried with the mutation the same haplotype most frequent in African populations ; Amerindian alleles D 9 D 1120 *9 and Diego A ; or Kell allele K were absent . HDL 2 in Venezuela had a low , but higher relative frequency (2 .6 %) than that in other Caucasoid populations . It should be searched first in choreic patients not having HTT mutations . The most likely remote ethnic origin for all detected families was African .