A locus for an axonal form of autosomal recessive Charcot-Marie-Tooth disease maps to chromosome 1q21.2q21.3
A locus for an axonal form of autosomal recessive Charcot-Marie-Tooth disease maps to chromosome 1q21.2q21.3
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DOI：
10.1086/302542
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发表时间：
1999-09-01
影响因子：
9.8
通讯作者：
LeGuern, E
中科院分区：
文献类型：
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作者：
Bouhouche, A;Benomar, A;LeGuern, E
Charcot-Marie-Tooth病(CMT)是一组影响周围神经系统的异质性疾病。常染色体显性遗传型轴索CMT(CMT2)有3个基因座已知，但尚未发现常染色体隐性遗传性轴索CMT(ARCMT2)。我们研究了一个有9个受影响同胞的摩洛哥ARCMT2大家族。所有表现为严重运动神经和感觉神经病变的患者在第二个十年内开始出现CMT，部分患者近端肌肉受累。排除已知的CMT2和ARCMT2基因座后，进行全基因组搜索。发现了与染色体IQ上的标记连锁的证据。根据多点LOD得分分析，标记D1S514、D1S2715、D1S2777和D1S2721的最大成对LOD得分高于阈值3.00，D1S2777、D1S2721和D1S2624基因座的最大成对LOD得分达到6.10。这些标记定义了一个纯合子区域，该区域将基因放置在4.4厘米的间隔内。此外，在未受影响的48岁个体中检测到的重组事件排除了D1S506标记，从而将间隔减少到1.7 cM。此外，PO基因由于其在染色体IQ上的位置和在髓鞘结构中的作用而被排除在外，通过物理定位和直接测序排除了它。
Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of disorders that affect the peripheral nervous system. Three loci are known for the autosomal dominant forms of axonal CMT (CMT2), but none have yet been identified for autosomal recessive axonal CMT (ARCMT2). We have studied a large consanguineous Moroccan ARCMT2 family with nine affected sibs. The onset of CMT was in the 2d decade in all affected individuals who presented with a severe motor and sensory neuropathy, with proximal muscle involvement occurring in some patients. After exclusion of known loci for CMT2 and for demyelinating ARCMT2, a genomewide search was performed. Evidence for linkage was found with markers on chromosome Iq. The maximum pairwise LOD score was above the threshold value of 3.00, for markers D1S514, D1S2715, D1S2777, and D1S2721, and it reached 6.10 at the loci D1S2777, D1S2721, and D1S2624, according to multipoint LOD-score analysis. These markers defined a region of homozygosity that placed the gene in a 4.4-cM interval. Moreover, a recombination event detected in an unaffected 48-year-old individual excludes the D1S506 marker, thereby reducing the interval to 1.7 cM. In addition, the PO gene, an attractive candidate because of both its location on chromosome Iq and its role in myelin structure, was excluded by physical mapping and direct sequencing.