A new mutation for Huntington disease following maternal transmission of an intermediate allele

Alicia Semaka, Chris Kay, Rene D. M. Belfroid, Emilia K. Bijlsma, Monique Losekoot, Irene M. van Langen, Merel C. van Maarle, Mayke Oosterloo, Michael R. Hayden, Martine J. van Belzen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


New mutations for Huntington disease (HD) originate from CAG repeat expansion of intermediate alleles (27-35 CAG). Expansions of such alleles into the pathological range (>= 36 CAG) have been exclusively observed in paternal transmission. We report the occurrence of a new mutation that defies the paternal expansion bias normally observed in HD. A maternal intermediate allele with 33 CAG repeats expanded in transmission to 48 CAG repeats causing a de novo case of HD in the family. Retrospectively, the mother presented with cognitive decline, but HD was never considered in the differential diagnosis. She was diagnosed with dementia and testing for HD was only performed after her daughter had been diagnosed. This observation of an intermediate allele expanding into the full penetrance HD range after maternal transmission has important implications for genetic counselling of females with intermediate repeats.
Original languageEnglish
Pages (from-to)28-30
JournalEuropean Journal of Medical Genetics
Issue number1
Publication statusPublished - Jan 2015


  • Huntington disease
  • Intermediate allele
  • New mutation
  • Maternal CAG repeat expansion
  • HTT gene

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