Clinical and molecular studies reveal a PSEN1 mutation (L153V) in a Peruvian family with early-onset Alzheimer's disease.
Clinical and molecular studies reveal a PSEN1 mutation (L153V) in a Peruvian family with early-onset Alzheimer's disease.
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DOI：
10.1016/j.neulet.2014.01.016
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发表时间：
2014-03-20
影响因子：
2.5
通讯作者：
Bird TD
中科院分区：
文献类型：
--
作者：
Cornejo-Olivas MR;Yu CE;Mazzetti P;Mata IF;Meza M;Lindo-Samanamud S;Leverenz JB;Bird TD
早老素1(PSEN1)基因突变在30%到70%的家族性早发性阿尔茨海默病(EOAD)病例中被发现(发病和60岁)。这些突变的流行程度是高度可变的，包括世界各地的种族差异。尚无家族性阿尔茨海默病(FAD)的秘鲁亲属被描述。标准化的临床评估和认知评估在一个患有严重Eoad的秘鲁家庭中完成。临床表现为起病早(35岁前)、进行性认知损害伴早期记忆丧失、空间定向障碍和执行功能障碍。我们对先证者PSEN1的所有外显子进行了测序，发现了一个C.475C>；G DNA突变，导致了该基因跨膜区2的p.L153V错义突变。这种突变也存在于另外三个受影响的兄弟姐妹中，但不存在于符合该突变与疾病分离的未受影响的家庭成员中。这是首次报道与PSEN1突变相关的受EoAD影响的秘鲁家庭。同样的突变以前在英国和法国家庭中也有报道，但一个非常接近突变和祖先信息标记分析的新变异表明，该突变可能起源于这个秘鲁家庭中的美洲印第安人或非洲人。
Presenilin 1 (PSEN1) gene mutations are found in 30 to 70% of familial early onset Alzheimer disease (EOAD) cases (onset <60 years). Prevalence of these mutations is highly variable including ethnic differences worldwide. No Peruvian kindred with familial AD (FAD) have been described. Standardized clinical evaluation and cognitive assessment was completed in a Peruvian family with severe EOAD. Clinical course was characterized by very early onset (before age 35 years), progressive cognitive impairment with early memory loss, spatial disorientation and executive dysfunction. We sequenced all exons of PSEN1 in the proband and identified a c.475C>G DNA change resulting in a p.L153V missense mutation in the transmembrane domain 2 of the gene. This mutation is also present in the three additional affected siblings but not in a non-affected family member consistent with segregation of this mutation with the disease. This is the first report of a Peruvian family affected with EOAD associated with a PSEN1 mutation. This same mutation has been reported previously in English and French families, but a novel variants very close to the mutation and ancestry informative markers analysis suggests the mutation might be of Amerindian or African origin in this Peruvian family.
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