Late-onset and typical Huntington disease families from Crete have distinct genetic origins

  • Authors:
    • Eleonora Kartsaki
    • Cleanthe Spanaki
    • Minas Tzagournissakis
    • Aphrodite Petsakou
    • Nicholas Moschonas
    • Marcy MacDonald
    • Andreas Plaitakis
  • View Affiliations

  • Published online on: February 1, 2006     https://doi.org/10.3892/ijmm.17.2.335
  • Pages: 335-346
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Abstract

HD families in which late-onset occurs consistently in affected members are rare. The objectives of this work was to study such late-onset HD families encountered on Crete, and to trace their genetic origin. Nine late-onset HD kindreds (61 affected members) were studied along with two typical HD families (17 affected members). We genotyped 33 late-onset Cretan HD chromosomes, 9 Cretan typical HD chromosomes and 114 Cretan control chromosomes using 14 STR markers and 20 SNPs that map to 4p16.3. In contrast to the typical HD pedigrees, the late-onset HD families lacked anticipation and juvenile cases. The expanded CAG repeat (36-42 units) in these families remained either stable or it showed small increment instability, even when transmitted through the father. All late-onset HD chromosomes shared a conserved haplotype defined by the markers D4S95: 1090, D4S127: 157, rs362277: A, rs3025814: G, rs2530596: A that span a 0.277-Mb segment on 4p16.3. Coalescence analysis traced this haplotype to a founder who lived about 1000 years ago. In contrast, each of the two typical HD disease pedigrees derived from a different founder. Sequencing of a 5-kb DNA segment immediately upstream of the HD gene revealed a novel single nucleotide polymorphism at −1757 bp relative to the translation start site, which was more prevalent in Cretan than in North American chromosomes. All late-onset HD families on Crete arose from a common founder with the disease's mutation evolving over the centuries via small-increment instability. These findings suggest that cis-acting factors may be operational.

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February 2006
Volume 17 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Kartsaki E, Spanaki C, Tzagournissakis M, Petsakou A, Moschonas N, MacDonald M and Plaitakis A: Late-onset and typical Huntington disease families from Crete have distinct genetic origins. Int J Mol Med 17: 335-346, 2006.
APA
Kartsaki, E., Spanaki, C., Tzagournissakis, M., Petsakou, A., Moschonas, N., MacDonald, M., & Plaitakis, A. (2006). Late-onset and typical Huntington disease families from Crete have distinct genetic origins. International Journal of Molecular Medicine, 17, 335-346. https://doi.org/10.3892/ijmm.17.2.335
MLA
Kartsaki, E., Spanaki, C., Tzagournissakis, M., Petsakou, A., Moschonas, N., MacDonald, M., Plaitakis, A."Late-onset and typical Huntington disease families from Crete have distinct genetic origins". International Journal of Molecular Medicine 17.2 (2006): 335-346.
Chicago
Kartsaki, E., Spanaki, C., Tzagournissakis, M., Petsakou, A., Moschonas, N., MacDonald, M., Plaitakis, A."Late-onset and typical Huntington disease families from Crete have distinct genetic origins". International Journal of Molecular Medicine 17, no. 2 (2006): 335-346. https://doi.org/10.3892/ijmm.17.2.335