A novel NGFB point mutation: a phenotype study of heterozygous patients
A novel NGFB point mutation: a phenotype study of heterozygous patients
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DOI：
10.1136/jnnp.2007.136051
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发表时间：
2009-02-01
影响因子：
11
通讯作者：
Solders, G.
中科院分区：
文献类型：
--
作者：
Minde, J.;Andersson, T.;Solders, G.
目的：最近描述了一个家族，其神经学表现类似于神经生长因子β（NGFB）基因点突变的遗传性感觉和自主神经病V型。纯合子基因型会导致残疾症状。本研究的目的是评估杂合子patients.Methods的症状：26例杂合子NGFB突变（12名男性，平均年龄50（13-90）岁）进行了临床检查，并回答了健康状况问卷，包括密歇根神经病筛查仪器（MNSI）。28名无突变的亲属（15名男性，平均年龄44（15-86）岁）作为临床检查部分的对照。23个杂合子进行了神经生理学检查和6个杂合子患者进行了腓肠神经biopsiz.Results：杂合子的表型范围从8例Charcot关节病开始在成年年龄和相关的神经病变的变量症状，但没有完全不敏感的疼痛，无汗或精神发育迟滞，到10个无症状的患者。年轻杂合子患者（55岁）与对照组之间的MNSI无差异。23例杂合子患者中有6例皮肤热感觉受损，23例患者中有11例有腕管综合征体征。腓肠神经活检显示小的有髓（Ad）和无髓（C）纤维中度减少。没有明显的相关性，小纤维减少symptoms.Conclusions：NGFB突变在其杂合子形式的结果在一个较轻的疾病比纯合子，具有可变的临床表现，从无症状的情况下，那些与夏科关节病出现在成年人的年龄。特别是年龄，但生活方式因素也可能影响临床多发性神经病的发展。
Objective: A family with neurological findings similar to hereditary sensory and autonomic neuropathy type V having a point mutation in the nerve growth factor beta (NGFB) gene was recently described. The homozygous genotype gives disabling symptoms. The purpose of the present study was to evaluate the symptoms in heterozygous patients.Methods: 26 patients heterozygous for the NGFB mutation (12 men, mean age 50 (13-90) years) were examined clinically and answered a health status questionnaire, including the Michigan Neuropathy Screening Instrument (MNSI). 28 relatives (15 men, mean age 44 (15-86) years) without the mutation served as controls in the clinical examination part. 23 of the heterozygotes were examined neurophysiologically and six heterozygous patients underwent a sural nerve biopsy.Results: The heterozygous phenotype ranged from eight patients with Charcot arthropathy starting in adult age and associated with variable symptoms of neuropathy but without complete insensitivity to pain, anhidrosis or mental retardation, to 10 symptom free patients. There was no difference in MNSI between the young heterozygous cases (, 55 years old) and the controls. Six of 23 heterozygous patients had impaired cutaneous thermal perception and 11 of 23 had signs of carpal tunnel syndrome. Sural nerve biopsies showed a moderate reduction of both small myelinated (Ad) and unmyelinated (C) fibres. No apparent correlation of small fibre reduction to symptoms was found.Conclusions: The NGFB mutation in its heterozygous form results in a milder disease than in homozygotes, with a variable clinical picture, ranging from asymptomatic cases to those with Charcot arthropathy appearing in adult age. Particularly age, but perhaps lifestyle factors also, may influence the development of clinical polyneuropathy.