PHENOTYPE OF CHROMOSOME 14-LINKED FAMILIAL ALZHEIMERS-DISEASE IN A LARGE KINDRED
PHENOTYPE OF CHROMOSOME 14-LINKED FAMILIAL ALZHEIMERS-DISEASE IN A LARGE KINDRED
复制标题
DOI：
10.1002/ana.410360308
复制
发表时间：
1994-09-01
影响因子：
11.2
通讯作者：
RASKIND, MA
中科院分区：
文献类型：
--
作者：
LAMPE, TH;BIRD, TD;RASKIND, MA
我们报告了14号染色体连锁家族性阿尔茨海默病(14qFAD)在L家族中的临床和神经病理特征。所有已知的16名患者的一些临床信息和6名家庭成员的详细神经病理结果可供查阅。L家系14qFAD表型的共同特征为：50岁前起病，早期进行性失语，提早出现肌阵挛和全身性发作，肌张力异常，皮质萎缩，大量广泛的老年斑和神经原纤维缠结，淀粉样血管病突出。最近定义的另外6个14q连锁FAD家系的表型特征可用描述：其中4个(Fad4、Fad2、A、B)的发现表明相对一致的14qFAD表型，与L家族的特殊临床和神经病理学特征密切一致。比较还发现了14qFAD的几个明显的表型变异：(1)在两个14q连锁的家系(SNW/FAD3，FAD1)中，在某些情况下，受影响的人可以活到70岁或更高，这两个家系的平均发病年龄(49岁)略高于他们的五个14qFAD同龄人(均为48岁)；(2)在SNW/FAD3家系中，所有10名受试者都没有癫痫发作和肌阵挛；(3)在几个14qFAD家系中和几个14qFAD家系中，不同程度地存在小脑淀粉样斑块。与最近在密码子717的淀粉样前体蛋白基因突变(即APP(717)FAD)的三个家系(TOR3、F19、ROM)中详细描述的表型特征的比较表明，几个区别：显著的进行性失语、肌阵挛、癫痫发作和副紧张症在APP(717)FAD中都明显不太常见，在最初的病程中主要是语言功能的保留。14Q连锁FAD的临床和神经病理表型的同质性和异质性程度及其与APP(717)FAD表型的可能有意义的区别有待进一步确定。
We report the clinical and neuropathological features of chromosome 14-linked familial Alzheimer's disease (14qFAD) in affected members of the L family. Some clinical information on all 16 known affected individuals and detailed neuropathological findings in 6 family members were available for review. Common features of the phenotype of 14qFAD in the L family included onset of dementia before the age of 50, early progressive aphasia, early-appearing myoclonus and generalized seizures, paratonia, cortical atrophy, numerous and extensive senile plaques and neurofibrillary tangles, and prominent amyloid angiopathy. Descriptions of phenotypic features were available for six additional recently defined 14q-linked FAD kindreds: the findings in four of them (FAD4, FAD2, A, B) indicated a relatively consistently shared 14qFAD phenotype, conforming closely with the specific clinical and neuropathological characteristics noted in the L family. Comparisons also suggested several ostensible phenotypic variants in 14qFAD: (1) In two 14q-linked kindreds (SNW/FAD3, FAD1), affected individuals in some instances were noted to survive to age 70 or beyond and the mean age at onset (> 49 years) in these two kindreds was somewhat higher than in their five 14qFAD counterparts (< 48 years in each); (2) in the SNW/FAD3 kindred, seizures and myoclonus were absent in all 10 subjects examined; and (3) cerebellar amyloid plaques were variably present within and among several 14qFAD kindreds. Comparisons with phenotypic features recently detailed in three kindreds (TOR3, F19, ROM) with codon 717 amyloid precursor protein gene mutations (i.e., APP(717) FAD) suggested several distinctions: Prominent progressive aphasia, myoclonus, seizures, and paratonia were all apparently less prevalent in APP(717) FAD, with language function predominantly spared over the initial disease course. The extent of homogeneity and heterogeneity in the clinical and neuropathological phenotype of 14q-linked FAD and its possible meaningful distinctions from the phenotypes of APP(717) FAD await further determination.