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Eur J Med Genet. 2015 Jan;58(1):28-30. doi: 10.1016/j.ejmg.2014.11.005. Epub 2014 Nov 20.

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

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Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada.
Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. Electronic address:


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.


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

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