Defective FA2H leads to a novel form of neurodegeneration with brain iron accumulation (NBIA).
Defective FA2H leads to a novel form of neurodegeneration with brain iron accumulation (NBIA).
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DOI：
10.1002/ana.22122
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发表时间：
2010-11
影响因子：
11.2
通讯作者：
Hayflick SJ
中科院分区：
文献类型：
--
作者：
Kruer MC;Paisán-Ruiz C;Boddaert N;Yoon MY;Hama H;Gregory A;Malandrini A;Woltjer RL;Munnich A;Gobin S;Polster BJ;Palmeri S;Edvardson S;Hardy J;Houlden H;Hayflick SJ
神经退行性疾病伴脑铁蓄积（NBIA）是一种独特的神经退行性疾病表型，已鉴定出几种致病基因。与NBIA基因突变相关的神经系统疾病的范围很广，其表型从婴儿神经变性和儿童期死亡到成人发作的帕金森病-肌张力障碍。在这里，我们报告了一个新的基因，导致NBIA的一种独特的形式的发现。使用同源性作图和候选基因测序，我们确定了脂肪酸羟化酶基因FA 2 H的突变，新牵连神经酰胺代谢异常的发病机制NBIA。神经影像学检查显示苍白球T2低信号，融合T2白色高信号，以及两个家族中受影响成员的严重脑桥小脑萎缩。表型上，受影响的家庭成员表现出痉挛性四肢轻瘫，共济失调和肌张力障碍，在儿童和发作性神经功能下降。与先前报道的PLA 2G 6类似，基于我们的发现和先前研究者的发现，FA 2 H突变的表型谱是多样的，因为FA 2 H突变已经在遗传性痉挛性截瘫（SPG 35）和进行性家族性脑白质营养不良中被鉴定。这些发现第一次将白色变性和NBIA联系起来，并暗示了NBIA发生中的新信号通路。
Neurodegeneration with brain iron accumulation (NBIA) represents a distinctive phenotype of neurodegenerative disease for which several causative genes have been identified. The spectrum of neurologic disease associated with mutations in NBIA genes is broad, with phenotypes that range from infantile neurodegeneration and death in childhood to adult-onset parkinsonism-dystonia. Here we report the discovery of a novel gene that leads to a distinct form of NBIA. Using autozygosity mapping and candidate gene sequencing, we identified mutations in the fatty acid hydroxylase gene FA2H, newly implicating abnormalities of ceramide metabolism in the pathogenesis of NBIA. Neuroimaging demonstrated T2 hypointensity in the globus pallidus, confluent T2 white matter hyperintensities, and profound pontocerebellar atrophy in affected members of two families. Phenotypically, affected family members exhibited spastic quadriparesis, ataxia, and dystonia with onset in childhood and episodic neurological decline. Analogous to what has been reported previously for PLA2G6, the phenotypic spectrum of FA2H mutations is diverse based on our findings and those of prior investigators, because FA2H mutations have been identified in both a form of hereditary spastic paraplegia (SPG35) and a progressive familial leukodystrophy. These findings link white matter degeneration and NBIA for the first time and implicate new signaling pathways in the genesis of NBIA.
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影响因子：
6
作者：
Galvin, JE;Giasson, B;Trojanowski, JQ
通讯作者：
Trojanowski, JQ
DOI：
10.1073/pnas.92.7.2539
发表时间：
1995-03-28
影响因子：
11.1
作者：
HARRIS, ZL;TAKAHASHI, Y;GITLIN, JD
通讯作者：
GITLIN, JD
DOI：
10.1196/annals.1306.021
发表时间：
2004-01-01
期刊：
REDOX-ACTIVE METALS IN NEUROLOGICAL DISORDERS
影响因子：
--
作者：
LeVine, SM;Chakrabarty, A
通讯作者：
Chakrabarty, A
影响因子：
9.8
作者：
Edvardson, Simon;Hama, Hiroko;Elpeleg, Orly
通讯作者：
Elpeleg, Orly
影响因子：
8.6
作者：
Schneider, Susanne A.;Paisan-Ruiz, Coro;Bhatia, Kailash P.
通讯作者：
Bhatia, Kailash P.