Whole genome analysis in a consanguineous family with early onset Alzheimer's disease

J. Clarimón*, R. Djaldetti, A. Lleó, R. J. Guerreiro, J. L. Molinuevo, C. Paisán-Ruiz, T. Gómez-Isla, R. Blesa, A. Singleton, J. Hardy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 SNP 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.

Original languageEnglish
Pages (from-to)1986-1991
Number of pages6
JournalNeurobiology of Aging
Volume30
Issue number12
DOIs
StatePublished - Dec 2009
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Autozygosity
  • Dementia
  • Early-onset
  • Genetics
  • Recessive

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