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

被引：21

作者：

Bras, Jose ^{[1
,2
,3
]}

Djaldetti, Ruth ^{[4
,5
,6
]}

Alves, Ana Margarida ^{[1
]}

Mead, Simon ^{[7
]}

Darwent, Lee ^{[1
]}

Lleo, Alberto ^{[8
,9
,10
]}

Luis Molinuevo, Jose ^{[11
,12
]}

Blesa, Rafael ^{[8
,9
]}

Singleton, Andrew ^{[13
]}

Hardy, John ^{[1
]}

Clarimon, Jordi ^{[8
,9
]}

Guerreiro, Rita ^{[1
,2
,3
]}

机构：

[1] UCL, Inst Neurol, Dept Mol Neurosci, 1 Wakefield St 1st Floor, London WC1N 1PJ, England

[2] Univ Aveiro, Dept Med Sci, Aveiro, Portugal

[3] Univ Aveiro, Inst Biomed iBiMED, Aveiro, Portugal

[4] Rabin Med Ctr, Dept Neurol, Beilinson Campus, Petah Tiqwa, Israel

[5] Felsenstein Res Ctr, Petah Tiqwa, Israel

[6] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel

[7] UCL, Inst Neurol, Dept Neurodegenerat Dis, MRC Prion Unit, London, England

[8] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, Memory Unit, Barcelona, Spain

[9] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, Barcelona, Spain

[10] Ctr Networked Biomed Res Neurodegenerat Dis, CIBERNED, Madrid, Spain

[11] Hosp Clin Barcelona, Inst Neurosci, Dept Neurol, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain

[12] Univ Barcelona, IDIBAPS, Barcelona, Spain

[13] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

来源：

NEUROBIOLOGY OF AGING | 2016年 / 46卷

基金：

英国医学研究理事会;

关键词：

Early onset Alzheimer's disease; Kufs disease; Recessive; Exome sequencing; Homozygosity; CTSF; KUFS-DISEASE; EXTENDED TRACTS; CANDIDATE GENES; GENOME ANALYSIS; FRAMEWORK;

D O I：

10.1016/j.neurobiolaging.2016.06.018

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：236.e1 / 236.e6

页数：6

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