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Neurobiol Aging. 2019 Aug 21. pii: S0197-4580(19)30293-3. doi: 10.1016/j.neurobiolaging.2019.08.015. [Epub ahead of print]

A unique common ancestor introduced P301L mutation in MAPT gene in frontotemporal dementia patients from Barcelona (Baix Llobregat, Spain).

Author information

1
BIOMICs Research Group, Lascaray Research Center, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain.
2
Neurology Department, Alzheimer's Disease and other Cognitive Disorders Unit, Hospital Clínic-IDIBAPS, Barcelona, Spain.
3
Neurological Tissue Bank of the Biobanc, Hospital Clínic-IDIBAPS, Barcelona, Spain.
4
Neurology Department, Hospital Universitario de Bellvitge, Barcelona, Spain.
5
Memory Clinic of Fundació ACE, Institut Catalá de Neurociències Aplicades, Barcelona, Spain.
6
Department of Neurology, Hospital Benito Menni, Sant Boi de Llobregat, Barcelona, Spain.
7
Unit of Neurology V and Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
8
Département de Neurologie, Centre de Référence des Démences Rares ou Précoces, Institute of Memory and Alzheimer's Disease, APHP, Centre Référent SLA, Hôpital Pitié-Salpêtrière, Paris, France; Institut du Cerveau et de la Moelle Épinière, Sorbonne Université, INSERM U1127, CNRS UMR 7225, Hôpital Pitié-Salpêtrière, Paris, France.
9
Département de Neurologie, Centre de Référence des Démences Rares ou Précoces, Institute of Memory and Alzheimer's Disease, APHP, Centre Référent SLA, Hôpital Pitié-Salpêtrière, Paris, France.
10
BIOMICs Research Group, Lascaray Research Center, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain. Electronic address: marian.mdepancorbo@ehu.eus.

Abstract

The County of Baix Llobregat (Barcelona, Catalonia, Spain) presents a high prevalence of familial frontotemporal dementia (FTD) in the presence of P301L mutation in the MAPT gene. To evaluate a possible unique founder effect of P301L, and its age, the analysis of 20 single-nucleotide polymorphisms covering 50 kb and 12 single-nucleotide polymorphisms located along 30 Mb around the mutation was performed by developing 2 multiplex single-base extension reactions. In addition, families with affected and healthy individuals from France and Italy were analyzed. The FTD-affected individuals from Barcelona carried the same 50-kb haplotype linked to P301L mutation, suggesting a unique common ancestor, as opposed to French patients. Italian patients are also probably descendants of a unique ancestor, which would be different from that of Barcelona. Diversity of 30-Mb haplotypes found in Barcelona and the inference of the mutation age in these populations, among other reasons, suggest that prevalence of FTD linked to P301L MAPT mutation is the result of a locally originated mutation.

KEYWORDS:

Common ancestor; Founder effect; Frontotemporal dementia FTD; MAPT; Mutational event; rs63751273

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