title: Evidence of a founder effect in families with frontotemporal dementia that harbor the tau +16 splice mutation.
abstract: The +16 exon 10 splice mutation of the tau gene (microtubule-associated protein tau, MAPT) has been reported in numerous families with frontotemporal dementia (FTD). To date, the majority of these families are from England and Wales in the UK, although families with this mutation have been reported from Australia and the USA. Our own analysis has identified eight families with the +16 MAPT splice mutation from around the Manchester and North Wales areas of the UK. Given the proximity of the UK families to one another it is likely that they are related and represent a single extended pedigree. In order to investigate this possibility, and the possibility that the families with this mutation from London, the USA, and Australia are related, we genotyped 11 microsatellite markers around the tau locus. In most cases (20/25, 80%), a common haplotype, approximately 3 cM in size, was identified. In the remaining cases, this haplotype appears to have been varyingly reduced in size by recombination. We demonstrate that the +16 mutation is on the H1 tau haplotype and that H1 specific polymorphisms are also shared by these families. These data provide evidence that the MAPT +16 splice mutation cases from around the world analyzed in this study are indeed related and represent a single pedigree that probably originated in the North Wales area of the UK. Furthermore, this single large pedigree may be of use in the identification of disease modifying loci in FTD.
authors.affiliation: Institute of Psychiatry, Section of Old Age Psychiatry, Denmark Hill, London, United Kingdom. s.pickering-brown@iop.kcl.ac.uk
authors.forename: Stuart
authors.initials: S
authors.lastname: Pickering-Brown
authors.forename: Matt
authors.initials: M
authors.lastname: Baker
authors.forename: Thomas
authors.initials: T
authors.lastname: Bird
authors.forename: John
authors.initials: J
authors.lastname: Trojanowski
authors.forename: Virginia
authors.initials: V
authors.lastname: Lee
authors.forename: Huw
authors.initials: H
authors.lastname: Morris
authors.forename: Martin
authors.initials: M
authors.lastname: Rossor
authors.forename: John C
authors.initials: JC
authors.lastname: Janssen
authors.forename: David
authors.initials: D
authors.lastname: Neary
authors.forename: David
authors.initials: D
authors.lastname: Craufurd
authors.forename: Anna
authors.initials: A
authors.lastname: Richardson
authors.forename: Julie
authors.initials: J
authors.lastname: Snowden
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: David
authors.initials: D
authors.lastname: Mann
authors.forename: Mike
authors.initials: M
authors.lastname: Hutton
mesh_terms: D001315:Australia; D003704:Dementia / Q000235:genetics*; D004739:England; D005260:Female; D018703:Founder Effect; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D014852:Wales; D016875:tau Proteins / Q000235:genetics*
chemical_list: D016875:tau Proteins