A gene for an autosomal recessive lower motor neuron disease with childhood onset maps to 1p36
A gene for an autosomal recessive lower motor neuron disease with childhood onset maps to 1p36
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DOI：
10.1212/01.wnl.0000223834.55225.2d
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发表时间：
2006-07-11
期刊：
影响因子：
9.9
通讯作者：
Viollet, L.
中科院分区：
文献类型：
--
作者：
Maystadt, I.;Zarhrate, M.;Viollet, L.
目的：描述一种儿童期发病的常染色体隐性下运动神经元病（LMND）新变异的临床特征，并定位致病基因。方法：作者在一个非洲大近亲家庭中进行了临床研究。在排除SMN1和SOD1位点的连锁后，他们进行了全基因组连锁分析，以绘制潜在的遗传缺陷。结果：这种具有儿童发病和常染色体隐性遗传模式的LMND的新变体的特点是一个渐进的对称和广泛的累及肌肉组织。5例患者中有4例自3岁起出现肌肉无力，儿童期严重恶化，成年后导致全身性四肢瘫痪。使用纯合子定位策略的遗传分析将该进行性广义LMND位点定位在染色体1p36上的D1S508和D1S2633位点之间3.9 cM（或1.5兆碱基）的间隔上（在D1S253位点θ = 0.00处Z(max) = 3.79）。该区域包含27个候选基因。结论：下运动神经元疾病一种新的罕见表型的遗传定位为鉴定位于1p36染色体区域的运动神经元变性的新基因开辟了道路。
Objective: To describe the clinical features of a novel variant of autosomal recessive lower motor neuron disease (LMND) with childhood onset and to map the disease-causing gene. Methods: The authors performed a clinical study in a large consanguineous African family. After linkage exclusion to SMN1 and SOD1 loci, they performed a genome-wide linkage analysis to map the underlying genetic defect. Results: This novel variant of LMND with childhood onset and autosomal recessive mode of inheritance is characterized by a progressive symmetric and generalized involvement of the musculature. Four of the five affected patients had muscle weakness since age 3, strongly worsening during childhood and leading to generalized tetraplegia in adulthood. Genetic analyses using homozygosity mapping strategy assigned this progressive generalized LMND locus to an interval of 3.9 cM (or 1.5 megabases) on chromosome 1p36, between loci D1S508 and D1S2633 (Z(max) = 3.79 at theta = 0.00 at locus D1S253). This region encloses 27 candidate genes. Conclusion: Genetic mapping of a novel rare phenotype of lower motor neuron disease opens the way toward the identification of a new gene involved in motor neuron degeneration, located in the 1p36 chromosomal region.