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. 2009 Apr 5;150B(3):425-9.
doi: 10.1002/ajmg.b.30826.

Repeat instability in the 27-39 CAG range of the HD gene in the Venezuelan kindreds: Counseling implications

D Brocklebank  1 , J Gayán, J M Andresen, S A Roberts, A B Young, S R Snodgrass, J B Penney, M A Ramos-Arroyo, J J Cha, H D Rosas, S M Hersch, A Feigin, S S Cherny, N S Wexler, D E Housman, L R Cardon; International-Venezuela Collaborative Research Group
Affiliations

Repeat instability in the 27-39 CAG range of the HD gene in the Venezuelan kindreds: Counseling implications

D Brocklebank et al. Am J Med Genet B Neuropsychiatr Genet. .

Abstract

The instability of the CAG repeat size of the HD gene when transmitted intergenerationally has critical implications for genetic counseling practices. In particular, CAG repeats between 27 and 35 have been the subject of debate based on small samples. To address this issue, we analyzed allelic instability in the Venezuelan HD kindreds, the largest and most informative families ascertained for HD. We identified 647 transmissions. Our results indicate that repeats in the 27-35 CAG range are highly stable. Out of 69 transmitted alleles in this range, none expand into any penetrant ranges. Contrastingly, 14% of alleles transmitted from the incompletely penetrant range (36-39 CAGs) expand into the completely penetrant range, characterized by alleles with 40 or more CAG repeats. At least 12 of the 534 transmissions from the completely penetrant range contract into the incompletely penetrant range of 36-39 CAG repeats. In these kindreds, none of the individuals with 27-39 CAGs were symptomatic, even though they ranged in age from 11 to 82 years. We expect these findings to be helpful in updating genetic counseling practices.

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Figures

FIG. 1
FIG. 1
Frequency distribution of trinucleotide repeat lengths in normal and HD chromosomes. Repeat lengths are defined as follows: Range I has fewer than 26 CAGs. As no changes were noted, Range I is not included for clarity. Range II has between 27and 35 CAGs and is the particular emphasis of our study. Range III has between 36 and 39 CAGs and is incompletely penetrant. Range IV has 40 or more CAGs and is completely penetrant.
FIG. 2
FIG. 2
Plot of repeat length change on transmission versus the originating parental repeat length, for paternal and maternal transmissions of alleles with 27 or more CAG repeats. The radius of the circle is proportional to the number of transmissions observed at each point. The smallest circle represents one observation and the largest circle represents 15 observations. A total of 268 paternal transmissions and 379 maternal transmissions were traced. Note that the scales of the plots for paternal and maternal transmissions differ.
See this image and copyright information in PMC

References

    1. Chong SS, Almqvist E, Telenius H, La Tray L, Nichol K, Bourdelat-Parks B, Goldberg YP, et al. Contribution of DNA sequence and CAG size to mutation frequencies of intermediate alleles for Huntington disease: Evidence from single sperm analyses. Hum Mol Genet. 1997;6:301–330. - PubMed
    1. Goldberg YP, Kremer B, Andrew SE, et al. Molecular analysis of new mutations for Huntington’s disease: Intermediate alleles and sex of origin effects. Nat Genet. 1993;5:174–179. - PubMed
    1. Goldberg YP, Andrew SE, Theilmann J, et al. Familial predisposition to recurrent mutations causing Huntington’s disease: Genetic risk to sibs of sporadic cases. J Med Gen. 1993;30:987–990. - PMC - PubMed
    1. Goldberg YP, McMurray CT, Zeisler J, Almqvist E, Sillence D, Richards F, Gacy AM, Buchanan J, Telenius H, Hayden MR. Increased instability of intermediate alleles in families with sporadic Huntington disease compared to similar sized intermediate alleles in the general population. Hum Mol Genet. 1995;4:1911–1918. - PubMed
    1. Gusella J, Wexler N, Conneally P, et al. A polymorphic DNA marker genetically linked to Huntington’s disease. Nature. 1983;306:234–238. - PubMed

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