Abstract:
:Alzheimer's disease (AD) is a genetically complex disorder for which the definite diagnosis is only accomplished postmortem. Mutations in 3 genes (APP, PSEN1, and PSEN2) are known to cause AD, but a large number of familial cases do not harbor mutations in these genes and several unidentified genes that contain disease-causing mutations are thought to exist. We performed whole exome sequencing in a Turkish patient clinically diagnosed with Alzheimer's disease from a consanguineous family with a complex history of neurological and immunological disorders and identified a mutation in NOTCH3 (p.R1231C), previously described as causing cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Complete screening of NOTCH3 in a cohort of 95 early onset AD cases and 95 controls did not reveal any additional pathogenic mutations. Although the complex history of disease in this family precluded us to establish segregation of the mutation found with disease, our results show that exome sequencing is a rapid, cost-effective and comprehensive tool to detect genetic mutations, allowing for the identification of unexpected genetic causes of clinical phenotypes. As etiological based therapeutics become more common, this method will be key in diagnosing and treating disease.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Guerreiro RJ,Lohmann E,Kinsella E,Brás JM,Luu N,Gurunlian N,Dursun B,Bilgic B,Santana I,Hanagasi H,Gurvit H,Gibbs JR,Oliveira C,Emre M,Singleton Adoi
10.1016/j.neurobiolaging.2011.10.009subject
Has Abstractpub_date
2012-05-01 00:00:00pages
1008.e17-23issue
5eissn
0197-4580issn
1558-1497pii
S0197-4580(11)00405-2journal_volume
33pub_type
杂志文章abstract::The knowledge base of nutrition and the brain is steadily expanding. Much of the research is aimed at ways to protect the brain from damage. In adults, the major causes of brain damage are aging and dementia. The most prominent dementia, and the condition that grabs the most public attention, is Alzheimer's disease. T...
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pub_type: 杂志文章,评审
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