Molecular basis of congenital insensitivity to pain with anhidrosis (CIPA):: Mutations and polymorphisms in TRKA (NTRK1) gene encoding the receptor tyrosine kinase for nerve growth factor
Molecular basis of congenital insensitivity to pain with anhidrosis (CIPA):: Mutations and polymorphisms in TRKA (NTRK1) gene encoding the receptor tyrosine kinase for nerve growth factor
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DOI：
10.1002/humu.1224
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发表时间：
2001-01-01
期刊：
影响因子：
3.9
通讯作者：
Indo, Y
中科院分区：
文献类型：
--
作者：
Indo, Y
先天性疼痛不敏感伴无汗症（CIPA），也称为遗传性感觉和自主神经病IV型（HSAN-IV），是一种常染色体隐性遗传性疾病，其特征为复发性阵发性发热、无汗（不能出汗）、对有害刺激无反应、自残行为和智力迟钝。TRKA（NTRK 1）基因位于1号染色体（1 q21-q22），由17个外显子组成，长度至少为23 kb。TRKA编码神经生长因子（NGF）的受体酪氨酸激酶（RTK），是负责CIPA的基因。在TRKA受体处的NGF信号转导缺陷导致不能支持交感神经节神经元和源自神经嵴的伤害性感觉神经元的存活。在不同国家的患者中鉴定的37种不同的TRKA突变，包括9种移码突变、7种无义突变、7种剪接突变和14种错义突变，分布在参与NGF结合的细胞外结构域以及细胞内信号转导结构域中。对CIPA突变和相关基因内多态性的广泛分析应有助于CIPA突变的检测，并有助于这种无痛但严重的遗传性疾病的诊断和遗传咨询。此外，自然发生。环TRKA错义突变与功能丧失提供了相当多的了解RTK家族的结构-功能关系。此外，CIPA的分子病理学将提供独特的机会来探索自主交感神经系统以及外周感觉神经系统在人类中传递有害刺激的关键作用。2001年，《突变》18：462-471。(C)2001 Wiley-Liss，Inc.
Congenital insensitivity to pain with anhidrosis (CIPA), also referred to as hereditary sensory and autonomic neuropathy type IV (HSAN-IV), is an autosomal recessive hereditary disorder characterized by recurrent episodic fever, anhidrosis (inability to sweat), absence of reaction to noxious stimuli, self mutilating behavior, and mental retardation. The TRKA (NTRK1) gene located on chromosome 1 (1q21-q22), consists of 17 exons and spans at least 23 kb. TRKA encodes the receptor tyrosine kinase (RTK) for nerve growth factor (NGF) and is the gene responsible for CIPA. Defects in NGF signal transduction at the TRKA receptor lead to failure to support survival of sympathetic ganglion neurons and nociceptive sensory neurons derived from the neural crest. Thirty,seven different TRKA mutations, identified in patients in various countries, including nine frameshift, seven nonsense, seven splice, and 14 missense mutations, are distributed in an extracellular domain involved in NGF binding, as well as in the intracellular signal-transduction domain. Extensive analysis of CIPA mutations and associated intragenic polymorphisms should facilitate detection of CIPA mutations and aid in the diagnosis and genetic counseling of this painless but severe genetic disorder with devastating complications. In addition, naturally occur. ring TRKA missense mutations with loss of function provide considerable insight into the structure-function relationship in the RTK family. Further, molecular pathology of CIPA would provide unique opportunities to explore critical roles of the autonomic sympathetic nervous system as well as peripheral sensory nervous system that transmit noxious stimuli in humans. Hum Mutat 18:462-471, 2001. (C) 2001 Wiley-Liss, Inc.