title: A new mutation for Huntington disease following maternal transmission of an intermediate allele.
abstract: 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.
authors.affiliation: Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada.
authors.forename: Alicia
authors.initials: A
authors.lastname: Semaka
authors.affiliation: Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Kay
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: René D M
authors.initials: RD
authors.lastname: Belfroid
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Emilia K
authors.initials: EK
authors.lastname: Bijlsma
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: Losekoot
authors.affiliation: Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Irene M
authors.initials: IM
authors.lastname: van Langen
authors.affiliation: Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Merel C
authors.initials: MC
authors.lastname: van Maarle
authors.affiliation: Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Mayke
authors.initials: M
authors.lastname: Oosterloo
authors.affiliation: Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: M.J.van_Belzen@lumc.nl.
authors.forename: Martine J
authors.initials: MJ
authors.lastname: van Belzen
mesh_terms: D000328:Adult; D000483:Alleles; D005220:Fathers; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics*; D008297:Male; D009035:Mothers; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins
keywords: HTT gene; Huntington disease; Intermediate allele; Maternal CAG repeat expansion; New mutation