Localization of a gene (CMT2A) for autosomal dominant Charcot-Marie-Tooth disease type 2 to chromosome 1p and evidence of genetic heterogeneity.
Localization of a gene (CMT2A) for autosomal dominant Charcot-Marie-Tooth disease type 2 to chromosome 1p and evidence of genetic heterogeneity.
复制标题
常染色体显性 2 型夏科-马里-图思病基因 (CMT2A) 定位于染色体 1p 以及遗传异质性的证据。
DOI：
10.1006/geno.1993.1334
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发表时间：
1993
期刊：
影响因子：
4.4
通讯作者：
Pericak-Vance,MA
中科院分区：
文献类型：
--
作者：
BenOthmane,K;Middleton,LT;Loprest,LJ;Wilkinson,KM;Lennon,F;Rozear,MP;Stajich,JM;Gaskell,PC;Roses,AD;Pericak-Vance,MA
腓骨肌萎缩症（CMT）2型（CMT 2）是一种遗传性周围神经病，其特征是发病年龄不同，神经传导速度正常或轻微降低。CMT2在病理学和遗传学上与CMT 1型（CMT1）不同。虽然CMT1已被证明是遗传异质性的，但尚未确定CMT2的染色体定位。我们已经进行了系谱连锁分析，在6个大的常染色体显性CMT2家族，并已证明连锁和异质性的一系列微卫星（D1S160，D1S170，D1S244，D1S228和D1S190）在远端区域的短臂1。使用混合物分析和两点lod评分发现了异质性的重要证据。使用标记物D1S244、D1S228和D1S199的多点结果的混合物分析支持两点结果。三个家庭，DUK662，DUK1241和1523给出的后验概率为1.0，0.98和0.88的连锁型。对“连锁”家族进行的多点分析表明，CMT2A基因最有利的位置位于D1S244和D1S228之间的区间内（位于该区间内与区间外的几率约为70：1）。这些结果表明，CMT2表型是继发于至少两个不同的基因，并证明在CMT表型进一步的异质性。
Charcot-Marie-Tooth (CMT) disease type 2 (CMT2) is an inherited peripheral neuropathy characterized by variable age of onset and normal or slightly diminished nerve conduction velocity. CMT2 is pathologically and genetically distinct from CMT type 1 (CMT1). While CMT1 has been shown to be genetically heterogeneous, no chromosomal localization has been established for CMT2. We have performed pedigree linkage analysis in six large autosomal dominant CMT2 families and have demonstrated linkage and heterogeneity to a series of microsatellites (D1S160, D1S170, D1S244, D1S228 and D1S190) in the distal region of the short arm of chromosome 1. Significant evidence for heterogeneity was found using admixture analysis and the two-point lod scores. Admixture analyses using the multipoint results for the markers D1S244, D1S228, and D1S199 supported the two-point findings. Three families, DUK662, DUK1241, and 1523 gave posterior probabilities of 1.0, 0.98, and 0.88 of being of the linked type. Multipoint analysis examining the "linked" families showed that the most favored location for the CMT2A gene is within the interval flanked by D1S244 and D1S228 (odds approximately 70:1 of lying within versus outside that interval). These findings suggest that the CMT2 phenotype is secondary to at least two different genes and demonstrate further heterogeneity in the CMT phenotype.