Estimating the probability of de novo HD cases from transmissions of expanded penetrant CAG alleles in the Huntington disease gene from male carriers of high normal alleles (27-35 CAG)

Am J Med Genet A. 2009 Jul;149A(7):1375-81. doi: 10.1002/ajmg.a.32901.

Abstract

Huntington disease (HD) is a dominantly transmitted neurodegenerative disorder that arises from expansion of a CAG trinucleotide repeat on chromosome 4p16.3. CAG repeat allele lengths are defined as fully penetrant at >or=40, reduced penetrance at 36-39, high normal at 27-35, and normal at <or=26. Fathers, but not mothers, with high normal alleles are at risk of transmitting potentially penetrant HD alleles (>or=36) to offspring. We estimated the conditional probability of an offspring inheriting an expanded penetrant allele given a father with a high normal allele by applying probability definitions and rules to estimates of HD incidence, paternal birth rate, frequency of de novo HD, and frequency of high normal alleles in the general population. The estimated probability that a male high normal allele carrier will have an offspring with an expanded penetrant allele ranges from 1/6,241 to 1/951. These estimates may be useful in genetic counseling for male high normal allele carriers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Genotype
  • Heterozygote*
  • Humans
  • Huntington Disease / epidemiology
  • Huntington Disease / genetics*
  • Inheritance Patterns / genetics*
  • Male
  • Middle Aged
  • Models, Genetic
  • Models, Statistical
  • Penetrance*
  • Trinucleotide Repeat Expansion / genetics*
  • Young Adult