Frontotemporal lobar degeneration with MAPT mutation in an Italian-Polish family. A case report.
Frontotemporal lobar degeneration with MAPT mutation in an Italian-Polish family. A case report.
复制标题
意大利-波兰家庭中伴有 MAPT 突变的额颞叶变性。
作者：
T. Wierzba;E. Lewandowska;J. Zaremba;M. Berdyński;C. Żekanowski;T. Stępień;P. Felczak;S. Tarka
额颞叶变性（FTLD）伴微管相关蛋白tau基因突变（FTLD伴MAPT突变）是一种具有多种临床表型的神经退行性疾病。我们介绍了一个意大利-波兰家庭，其MAPT基因IVS10+3G> a突变与男性先证（图2，II.2， H1s/H1b二倍型）和他的妹妹（图2，II.1， H1s/H1j二倍型）的H1s单倍型相关。本报告介绍了先证者及其患病妹妹的临床、神经病理学和基因检测，这两个成员来自一个由25个家庭成员组成的意大利-波兰家庭。他们的临床病史包括痴呆、运动和心血管疾病。磁共振成像显示额叶和颞叶脑萎缩。脑样本的神经病理学研究显示神经元丢失，胶质细胞形成，神经原纤维缠结的发生，大量的神经丝，盘绕体和大量的tau蛋白沉积，包括神经元和胶质细胞中的3-和4-重复亚型。仅在男性先证脑中，海马颗粒神经元中存在匹克体样沉积物。两例均见血管壁病变。在超微结构上，男性先证者显示胶原纤维团簇，主要位于周细胞位置。除了典型的神经原纤维病理外，星形胶质细胞中还描述了聚集的胶质纤维丝和脂褐质沉积。我们的报告表明，伴有IVS10+3G>A MAPT突变的FTLD主要对中枢神经系统造成损害，并诱导神经病理改变，这取决于MAPT的单倍型。在本病的临床过程中，也可观察到心血管系统的损害。
Frontotemporal lobar degeneration (FTLD) with mutations in the MAPT (microtubule-associated protein tau) gene (FTLD with MAPT mutation) is a neurodegenerative disease with various clinical phenotypes. We present an Italian- Polish family with a IVS10+3G>A mutation in the MAPT gene, linked with haplotype H1s in a male proband (Fig. 2, II.2, H1s/H1b diplotype) and his sister (Fig. 2, II.1, the H1s/H1j diplotype). This report presents clinical, neuropathological and genetic testing of the proband and his affected sister, two members of an Italian-Polish family consisting of 25 family members. Their clinical history includes dementia as well as movement and cardiovascular disorders. Magnetic resonance imaging showed frontal and temporal cerebral atrophy. Neuropathological studies of the brain samples showed loss of neurons, gliosis, and the occurrence of neurofibrillary tangles, numerous neuropil threads, coiled bodies and abundant deposits of tau protein, including 3- and 4-repeated isoforms in neurons and glial cells. Only in the male proband brain, there were Pick body-like deposits in granule neurons of the hippocampus. Pathology of vascular walls was found in both cases. Ultrastructurally, the male proband showed clusters of collagen fibers mainly in a pericyte position. Beside the typical neurofibrillary pathology, aggregated gliofilaments and lipofuscin deposits in astroglia are described. Our report suggests that FTLD with IVS10+3G>A MAPT mutation causes damage mainly to the central nervous system and induces neuropathological changes, depending on the haplotypes of MAPT. In the clinical course of this disease, damage of the cardiovascular system may also be observed.
登录
查看更多内容
17 号染色体连锁痴呆。
DOI：
10.1007/s000180050221
发表时间：
1998
期刊：
Cellular and molecular life sciences : CMLS.
影响因子：
--
作者：
Wilhelmsen,KC
通讯作者：
Wilhelmsen,KC
影响因子：
6
作者：
Cairns, Nigel J.;Neumann, Manuela;Mackenzie, Ian R. A.
通讯作者：
Mackenzie, Ian R. A.
DOI：
10.1073/pnas.95.13.7737
发表时间：
1998-06-23
影响因子：
11.1
作者：
Spillantini, MG;Murrell, JR;Ghetti, B
通讯作者：
Ghetti, B
DOI：
10.1152/ajplung.00447.2004
发表时间：
2005-07-01
影响因子：
4.9
作者：
Birukova, AA;Birukov, KG;Verin, AD
通讯作者：
Verin, AD