NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia (SPG6)
NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia (SPG6)
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DOI：
10.1086/378817
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发表时间：
2003-10-01
影响因子：
9.8
通讯作者：
Fink, JK
中科院分区：
文献类型：
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作者：
Rainier, S;Chai, JH;Fink, JK
遗传性痉挛截瘫(HSPs)是一种以进行性肢体无力和痉挛为特征的遗传异质性疾病。其分子发病机制目前知之甚少。我们报道在一个常染色体显性遗传性HSP(ADHSP)家系中发现了NIPA1基因的显性负突变，该突变与染色体15q11-q13(SPG6基因座)连锁；在一个与ADHSP无关的家系中发现了完全相同的突变，该突变太小，无法进行有意义的连锁分析。NIPA1在神经元组织中高度表达，编码一种可能的膜转运蛋白或受体。鉴定NIPA1的功能和配体将有助于理解HSP的轴突神经变性，并可能具有重要的治疗意义。
The hereditary spastic paraplegias (HSPs) are genetically heterogeneous disorders characterized by progressive lower-extremity weakness and spasticity. The molecular pathogenesis is poorly understood. We report discovery of a dominant negative mutation in the NIPA1 gene in a kindred with autosomal dominant HSP (ADHSP), linked to chromosome 15q11-q13 (SPG6 locus); and precisely the same mutation in an unrelated kindred with ADHSP that was too small for meaningful linkage analysis. NIPA1 is highly expressed in neuronal tissues and encodes a putative membrane transporter or receptor. Identification of the NIPA1 function and ligand will aid an understanding of axonal neurodegeneration in HSP and may have important therapeutic implications.