| The C9ORF72 expansion mutation is a common cause of ALS+/-FTD in Europe and has a single founder. | |
| | |
MedLine Citation:
|
PMID: 22692064 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
A massive hexanucleotide repeat expansion mutation (HREM) in C9ORF72 has recently been linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we describe the frequency, origin and stability of this mutation in ALS+/-FTD from five European cohorts (total n=1347). Single-nucleotide polymorphisms defining the risk haplotype in linked kindreds were genotyped in cases (n=434) and controls (n=856). Haplotypes were analysed using PLINK and aged using DMLE+. In a London clinic cohort, the HREM was the most common mutation in familial ALS+/-FTD: C9ORF72 29/112 (26%), SOD1 27/112 (24%), TARDBP 1/112 (1%) and FUS 4/112 (4%) and detected in 13/216 (6%) of unselected sporadic ALS cases but was rare in controls (3/856, 0.3%). HREM prevalence was high for familial ALS+/-FTD throughout Europe: Belgium 19/22 (86%), Sweden 30/41 (73%), the Netherlands 10/27 (37%) and Italy 4/20 (20%). The HREM did not affect the age at onset or survival of ALS patients. Haplotype analysis identified a common founder in all 137 HREM carriers that arose around 6300 years ago. The haplotype from which the HREM arose is intrinsically unstable with an increased number of repeats (average 8, compared with 2 for controls, P<10(-8)). We conclude that the HREM has a single founder and is the most common mutation in familial and sporadic ALS in Europe.European Journal of Human Genetics advance online publication, 13 June 2012; doi:10.1038/ejhg.2012.98. |
| | |
Authors:
|
Bradley N Smith; Stephen Newhouse; Aleksey Shatunov; Caroline Vance; Simon Topp; Lauren Johnson; Jack Miller; Younbok Lee; Claire Troakes; Kirsten M Scott; Ashley Jones; Ian Gray; Jamie Wright; Tibor Hortobágyi; Safa Al-Sarraj; Boris Rogelj; John Powell; Michelle Lupton; Simon Lovestone; Peter C Sapp; Markus Weber; Peter J Nestor; Helenius J Schelhaas; Anneloor Alm Ten Asbroek; Vincenzo Silani; Cinzia Gellera; Franco Taroni; Nicola Ticozzi; Leonard Van den Berg; Jan Veldink; Phillip Van Damme; Wim Robberecht; Pamela J Shaw; Janine Kirby; Hardev Pall; Karen E Morrison; Alex Morris; Jacqueline de Belleroche; J M B Vianney de Jong; Frank Baas; Peter M Andersen; John Landers; Robert H Brown; Michael E Weale; Ammar Al-Chalabi; Christopher E Shaw |
Related Documents
:
|
22607024 - Tgfb1 genetic polymorphisms and coronary heart disease risk: a meta-analysis. 22878964 - P.r4810k, a polymorphism of rnf213, the susceptibility gene for moyamoya disease, is as... 22403584 - Generation of a multi-locus chicken introgression line to study the effects of genetic ... 22384374 - Glypican gene gpc5 participates in the behavioral response to ethanol: evidence from hu... 11502364 - Genetic polymorphism in the cathepsin g gene and the risk of alzheimer's disease. 19558534 - Phenotypic characteristics of familial glucocorticoid deficiency (fgd) type 1 and 2. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-6-13 |
Journal Detail:
|
Title: European journal of human genetics : EJHG Volume: - ISSN: 1476-5438 ISO Abbreviation: - Publication Date: 2012 Jun |
Date Detail:
|
Created Date: 2012-6-13 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9302235 Medline TA: Eur J Hum Genet Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Department of Clinical Neurosciences, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, Kings College London, London, UK. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Aniridia.
Next Document: Agenesis of the corpus callosum and gray matter heterotopia in three patients with constitutional mi...