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J7 Intermediate allele expansion leads to huntington’s disease expression in large kindred
  1. Hope Heller1,
  2. Jan Blancato2,
  3. Thomas Cummings1,
  4. Fahd Amjad1,
  5. Ira Shoulson2,
  6. Fernando Pagan1,
  7. Karen Anderson2
  1. 1Medstar Georgetown University Hospital, Washington, DC, USA
  2. 2Georgetown University, Washington, DC, USA


Background Huntington’s disease is a progressive autosomal dominant genetic disorder characterised by variable motor, cognitive, and psychiatric symptoms. The mean age of onset is 35–44 years.1 Clinical expression is associated with a trinucleotide repeat expansion, 36 or more CAG trinucleotide repeats in HTT gene on chromosome 4.

Case history A 39 year old Caucasian female with apparent HD was referred to our clinic for diagnosis and treatment. It was reported that she experienced onset of psychiatric symptoms in her early 30s and chorea at age 35. There was no family history of HD in a sibship of 15 individuals, 5 older than her. DNA testing revealed CAG repeat alleles of 47 and 24, consistent with the clinical diagnosis of HD. The proband’s parents were DNA tested and her 72 y/o asymptomatic father had alleles of 32/17 and her 65 year old mother had CAG repeat alleles of 24/15. Two of the proband’s siblings underwent DNA testing and found to have the normal paternal allele.

Conclusion These data support the hypothesis that the paternal intermediate allele (IA) of 32 CAG repeats, a moderate risk allele for disease causing expansion in offspring,2 was expanded to an unprecedented number in the fertilisation event involving our patient. Genetic counselling and DNA testing for “at risk” offspring is ongoing with two normal DNA results of 17/15 having been reported in two of the siblings. DNA testing on paternal buccal cells is ongoing to rule out somatic mosaicism. Clinical and psychological evaluation of the IA carrier is in progress.


  1. Warby, et al. Genetests 2014

  2. Smelka, et al.

  • Intermediate Allele

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