Xia Mingrong, Chen Shuai, Shi Yingying, Huang Yue, Xu Junling, Zhao Ting, He Shuang, Wu Yingying, Xu Changshui, Zang Weizhou, Zhang Jiewen
Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Radiology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Neurobiol Aging. 2015 Dec;36(12):3334.e13-3334.e18. doi: 10.1016/j.neurobiolaging.2015.09.003. Epub 2015 Sep 8.
We describe a probably novel mutation in exon 5 of the presenilin 2 gene (Pro123Leu) in a Chinese familial early-onset Alzheimer's disease, which clinically manifests as progressive memory loss, cognitive impairment, parkinsonism, and myoclonic jerks. Clinical and neuroimaging examination, target region capture, and high-throughput sequencing were performed in a family of 4 generations. Cerebral perfusion and glucose metabolism were evaluated using arterial spin labeling perfusion magnetic resonance imaging and (18)F-fludeoxyglucose positron emission tomography, respectively. Target region capture sequencing yielded a novel missense mutation at codon 123 (P123L) which is a heterozygous C to T point mutation at position 368 (c.368C>T) in exon 5 of the presenilin 2 leading to a proline-to-leucine substitution. The results were also identified by Sanger sequencing in 7 family members but not in the other 9 unaffected family members and 100 control subjects. This mutation is probably pathogenic and is the first of its kind reported in an early-onset familial AD associated with atypical symptom presentation.
我们描述了在中国一个早发性家族性阿尔茨海默病患者中早老素2基因第5外显子的一个可能的新突变（Pro123Leu），该疾病临床上表现为进行性记忆丧失、认知障碍、帕金森综合征和肌阵挛。对一个四代家族进行了临床和神经影像学检查、目标区域捕获及高通量测序。分别使用动脉自旋标记灌注磁共振成像和（18）F-氟脱氧葡萄糖正电子发射断层扫描评估脑灌注和葡萄糖代谢。目标区域捕获测序在第123密码子处产生了一个新的错义突变（P123L），这是早老素2基因第5外显子中第368位（c.368C>T）的一个杂合性C到T点突变，导致脯氨酸被亮氨酸取代。7名家族成员经桑格测序也鉴定出该结果，但在其他9名未受影响的家族成员和100名对照受试者中未发现。该突变可能具有致病性，是在伴有非典型症状表现的早发性家族性阿尔茨海默病中报道的首例此类突变。
