Rudenskaya G E, Petukhova M S, Zabnenkova V V, Cherevatova T B, Ryzhkova O P
Research Centre for Medical Genetics, Moscow, Russia.
Zh Nevrol Psikhiatr Im S S Korsakova. 2023;123(11):120-127. doi: 10.17116/jnevro2023123111120.
A familial case of a rare autosomal dominant Alzheimer's disease (AD), related to gene (AD3, OMIM 607822), differing from common multifactorial form by earlier onset and, in part of cases, by accompanying neurological signs, spastic paraparesis particularly, is presented. The first sign in a female proband and in her son was paraparesis manifested at the age of 29 and 21 years, respectively. Cognitive disturbances developed soon; the former diagnosis was hereditary spastic paraplegia with cognitive impairment, In the proband examined in 2008 at 33 years old the diagnosis was not established. In the son examined in 2022 at 27 years old whole-exome sequencing detected a novel missense mutation p.Thr421Ala. The mutation was confirmed by Sanger sequencing in him, found out in the proband (who was severely disabled by that time) and excluded in her unaffected mother. Except for different age of onset, AD3 in two patients was similar, though in whole it is variable, also in relatives. The variability and rareness of the disease hampers clinical diagnostics. Massive parallel sequencing is a most reliable diagnostic method.
本文报告了一例罕见的常染色体显性阿尔茨海默病（AD）家族病例，该病例与 基因（AD3，OMIM 607822）相关，与常见的多因素形式不同，其发病较早，部分病例伴有神经体征，尤其是痉挛性截瘫。先证者为一名女性，其首发症状为截瘫，分别出现在29岁和21岁时，她的儿子也是如此。随后很快出现认知障碍；之前的诊断为伴有认知障碍的遗传性痉挛性截瘫。2008年对33岁的先证者进行检查时未明确诊断。2022年对27岁的儿子进行检查时，全外显子组测序检测到一个新的错义突变p.Thr421Ala。该突变在他身上经桑格测序得到证实，在先证者（当时已严重残疾）身上也被发现，而在其未受影响的母亲身上被排除。除了发病年龄不同外，两名患者的AD3情况相似，不过总体而言该病具有变异性，在亲属中也是如此。该病的变异性和罕见性阻碍了临床诊断。大规模平行测序是最可靠的诊断方法。
