Maystadt I, Zarhrate M, Leclair-Richard D, Estournet B, Barois A, Renault F, Routon M-C, Durand M-C, Lefebvre S, Munnich A, Verellen-Dumoulin C, Viollet L
Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393, Hôpital Necker Enfants Malades, 149 rue de Sèvres, F-75743 Paris Cedex 15, France.
Neurology. 2006 Jul 11;67(1):120-4. doi: 10.1212/01.wnl.0000223834.55225.2d. Epub 2006 May 25.
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.
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.
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.
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.
描述一种常染色体隐性遗传性儿童期起病的下运动神经元病（LMND）新变异型的临床特征，并对致病基因进行定位。
作者对一个非洲近亲大家族进行了临床研究。在排除与SMN1和SOD1基因座的连锁关系后，他们进行了全基因组连锁分析以定位潜在的基因缺陷。
这种儿童期起病、常染色体隐性遗传模式的LMND新变异型的特征是肌肉组织进行性对称性全身受累。五名受影响患者中有四名自3岁起出现肌肉无力，在儿童期病情严重恶化，成年后导致全身四肢瘫痪。使用纯合性定位策略进行的基因分析将这种进行性全身LMND基因座定位于1号染色体p36上3.9厘摩（或150万个碱基对）的区间内，位于基因座D1S508和D1S2633之间（在基因座D1S253处，θ = 0.00时Z（max） = 3.79）。该区域包含27个候选基因。
下运动神经元病一种新型罕见表型的基因定位为鉴定位于1p36染色体区域、参与运动神经元变性的新基因开辟了道路。
