Brooks W S, Kwok J B J, Halliday G M, Godbolt A K, Rossor M N, Creasey H, Jones A O, Schofield P R
Prince of Wales Medical Research Institute, University of New South Wales, Barker Street, Randwick, Sydney, NSW 2031, Australia.
Neurology. 2004 Nov 9;63(9):1613-7. doi: 10.1212/01.wnl.0000142965.10778.c7.
Most mutations in the amyloid precursor protein (APP) gene have been associated with familial Alzheimer disease (AD); however, some mutations within the Abeta-coding sequence have been described in families with recurrent cerebral hemorrhage. The APPAla692Gly (Flemish) mutation was reported in a family in which affected members developed hemorrhagic stroke, progressive dementia, or both.
To describe clinical, neuropathologic, and genetic features of a family of British origin with the Flemish APP mutation.
Clinical features of the proband and two affected relatives were obtained by history, examination, and medical record review. Some information on deceased affected relatives was obtained by informant interview. Neuropathologic examination was carried out on one case. DNA studies were carried out on three affected and three unaffected individuals.
Presenile dementia was present in a pattern consistent with dominant inheritance, with the APP692 mutation being found in all affecteds and no unaffecteds. The proband also had a cerebral hemorrhage, but was the only one of five affecteds to have this complication. Neuropathologic examination confirmed AD, congophilic angiopathy, and hemorrhagic infarction.
This expands the number of families reported with mutations in the coding region of the amyloid precursor protein gene. Cerebral hemorrhage appears to be less frequent in this family than in the previously reported Flemish pedigree with the same mutation.
淀粉样前体蛋白（APP）基因的大多数突变与家族性阿尔茨海默病（AD）相关；然而，在复发性脑出血家族中已描述了一些β淀粉样蛋白编码序列内的突变。APP Ala692Gly（佛兰芒）突变在一个家族中被报道，该家族中受影响成员发生出血性中风、进行性痴呆或两者皆有。
描述一个具有佛兰芒APP突变的英裔家族的临床、神经病理学和遗传学特征。
通过病史、检查和病历回顾获取先证者及两名受影响亲属的临床特征。通过 informant 访谈获取了一些关于已故受影响亲属的信息。对一例进行了神经病理学检查。对三名受影响个体和三名未受影响个体进行了 DNA 研究。
早老性痴呆呈符合显性遗传的模式，在所有受影响者中发现了APP692突变，未受影响者中未发现。先证者也发生了脑出血，但在五名受影响者中是唯一出现这种并发症的。神经病理学检查证实为AD、嗜刚果红血管病和出血性梗死。
这增加了报道的淀粉样前体蛋白基因编码区突变家族的数量。该家族中脑出血的发生率似乎低于先前报道的具有相同突变的佛兰芒家系。
