Novel frameshift and splice site mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) associated with hereditary sensory neuropathy type IV
Novel frameshift and splice site mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) associated with hereditary sensory neuropathy type IV
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DOI：
10.1016/j.nmd.2005.10.007
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发表时间：
2006-01-01
影响因子：
2.8
通讯作者：
Nelis, E
中科院分区：
文献类型：
--
作者：
Verpoorten, N;Claeys, KG;Nelis, E
先天性疼痛不敏感伴无汗症或遗传性感觉和自主神经病变IV型（HSAN IV）是第一个涉及神经营养因子信号转导途径的人类遗传性疾病。HSAN IV的特征是对伤害性刺激没有反应，反复发作发热，无汗，自残行为和通常的精神发育迟滞。1型神经营养酪氨酸激酶受体（NTRK1）的突变与这种疾病有关。我们报告了4例HSAN IV患者的4个纯合突变，2个移码突变（p.Gln626fsX6和p.Gly181fsX58），1个错义突变（p.Arg761Trp）和1个剪接位点突变（c.359+5G>T）。剪接位点突变导致患者mRNA中外显子2和3的跳跃，导致第二个富含亮氨酸的基序的框内缺失。NTRK1突变在欧洲人群中很少报告。该报告扩展了在诊断为HSAN IV的患者中观察到的NTRK1突变谱。(C)2005 Elsevier B.V.保留所有权利。
Congenital insensitivity to pain with anhidrosis or hereditary sensory and autonomic neuropathy type IV (HSAN IV) is the first human genetic disorder implicated in the neurotrophin signal transduction pathway. HSAN IV is characterized by absence of reaction to noxious stimuli, recurrent episodes of fever, anhidrosis, self-mutilating behavior and often mental retardation. Mutations in the neurotrophic tyrosine kinase, receptor, type 1 (NTRK1) are associated with this disorder. Here we report four homozygous mutations, two frameshift (p.Gln626fsX6 and p.Gly181fsX58), one missense (p.Arg761Trp) and one splice site (c.359+5G>T) mutation in four HSAN IV patients. The splice site mutation caused skipping of exons 2 and 3 in patient's mRNA resulting in an in-frame deletion of the second leucine-rich motif. NTRK1 mutations are only rarely reported in the European population. This report extends the spectrum of NTRK1 mutations observed in patients diagnosed with HSAN IV. (C) 2005 Elsevier B.V. All rights reserved.