Exome sequencing in a consanguineous family clinically diagnosed with early-onset Alzheimer's disease identifies a homozygous CTSF mutation

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• 作者：Jose Bras^a ; ^b ; Ruth Djaldetti^c ; ^d ; Ana Margarida Alves^a ; Simon Mead^e ; Lee Darwent^a ; Alberto Lleo^f ; ^g ; Jose Luis Molinuevo^h ; Rafael Blesa^f ; Andrew Singletonⁱ ; John Hardy^a ; Jordi Clarimon^f ; Rita Guerreiro^a ; ^b ; ^{r.guerreiro@ucl.ac.uk" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Early onset Alzheimer's disease ; Kufs disease ; Recessive ; Exome sequencing ; Homozygosity ; CTSF
• 刊名：Neurobiology of Aging
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：46
• 期：Complete
• 页码：236.e1-236.e6
• 全文大小：1084 K

文摘

We have previously reported the whole genome genotyping analysis of 2 consanguineous siblings clinically diagnosed with early onset Alzheimer's disease (AD). In this analysis, we identified several large regions of homozygosity shared between both affected siblings, which we suggested could be candidate loci for a recessive genetic lesion underlying the early onset AD in these cases. We have now performed exome sequencing in one of these siblings and identified the potential cause of disease: the CTSF c.1243G>A:p.Gly415Arg mutation in homozygosity. Biallelic mutations in this gene have been shown to cause Type B Kufs disease, an adult-onset neuronal ceroid lipofuscinosis with some cases resembling the impairment seen in AD.