Whole genome analysis in a consanguineous family with early onset Alzheimer's disease
Por:
Clarimon, J, Djaldetti, R, Lleo, A, Guerreiro, RJ, Molinuevo, JL, Paisan-Ruiz, C, Gomez-Isla, T, Blesa, R, Singleton, A, Hardy, J
Publicada:
1 dic 2009
Resumen:
Early-onset. Alzheimer's disease (EOAD) is a clinically and genetically heterogeneous condition in which the typical features appear significantly earlier in life (before 65 years). Mutations in three genes (PSEN1, PSEN2, and APP) have been identified in autosomal dominant forms of EOAD. However, in about 50% of Mendelian cases and in most of the sporadic EOAD patients, no mutations have been found. We present clinical characteristics of an Israeli family comprising two affected siblings with EOAD born to neurologically healthy parents who were first cousins (both parents died after 90 years old). Sequence analysis of PSEN1, PSEN2, APP, TAU, PGRN, and PRNP failed to reveal any mutations in the affected siblings. Because the disease in this family is consistent with an autosomal recessive mode of inheritance we identified all homozygous regions identical by descent (IBD) in both siblings, by high-density SKIP genotyping. We provide here the first catalog of autozygosity in EOAD and suggest that the regions identified are excellent candidate loci for a recessive genetic lesion causing this disease. (C) 2008 Elsevier Inc. All rights reserved.
Filiaciones:
Clarimon, J:
Hosp Santa Creu & Sant Pau, Dept Neurol, Alzheimers Lab, Memory Unit, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, CIBERNED, Barcelona 08025, Spain
Djaldetti, R:
Rabin Med Ctr, Dept Neurol, Petah Tiqwa, Israel
Felsenstein Res Ctr, Petah Tiqwa, Israel
Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel
Lleo, A:
Hosp Santa Creu & Sant Pau, Dept Neurol, Alzheimers Lab, Memory Unit, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, CIBERNED, Barcelona 08025, Spain
Guerreiro, RJ:
NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal
Molinuevo, JL:
Hosp Clin & Univ Barcelona, Inst Neurosci, Dept Neurol, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain
Paisan-Ruiz, C:
NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England
Inst Neurol, Reta Lila Weston Labs, London WC1N 3BG, England
Gomez-Isla, T:
Hosp Santa Creu & Sant Pau, Dept Neurol, Alzheimers Lab, Memory Unit, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, CIBERNED, Barcelona 08025, Spain
Blesa, R:
Hosp Santa Creu & Sant Pau, Dept Neurol, Alzheimers Lab, Memory Unit, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, CIBERNED, Barcelona 08025, Spain
Singleton, A:
NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
Hardy, J:
Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England
Inst Neurol, Reta Lila Weston Labs, London WC1N 3BG, England
Open Access
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