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

被引：12

作者：

Semaka, Alicia ^{[1
]}

Kay, Chris ^{[1
]}

Belfroid, Rene D. M. ^{[2
]}

Bijlsma, Emilia K. ^{[2
]}

Losekoot, Monique ^{[2
]}

van Langen, Irene M. ^{[3
]}

van Maarle, Merel C. ^{[4
]}

Oosterloo, Mayke ^{[5
,6
]}

Hayden, Michael R. ^{[1
]}

van Belzen, Martine J. ^{[2
]}

机构：

[1] Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 1M9, Canada

[2] Leiden Univ, Med Ctr, Dept Clin Genet, NL-2300 RC Leiden, Netherlands

[3] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands

[4] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands

[5] Maastricht Univ, Med Ctr, Dept Neurol, Maastricht, Netherlands

[6] Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RC Leiden, Netherlands

来源：

EUROPEAN JOURNAL OF MEDICAL GENETICS | 2015年 / 58卷 / 01期

基金：

加拿大健康研究院;

关键词：

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

D O I：

10.1016/j.ejmg.2014.11.005

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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. (C) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：28 / 30

页数：3

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