Kovach M J, Lin J P, Boyadjiev S, Campbell K, Mazzeo L, Herman K, Rimer L A, Frank W, Llewellyn B, Jabs E W, Gelber D, Kimonis V E
Division of Genetics and Metabolism, Department of Pediatrics, Southern Illinois University School of Medicine, Springfield, IL 62794-9658, USA.
Am J Hum Genet. 1999 Jun;64(6):1580-93. doi: 10.1086/302420.
Charcot-Marie-Tooth disease (CMT) with deafness is clinically distinct among the genetically heterogeneous group of CMT disorders. Molecular studies in a large family with autosomal dominant CMT and deafness have not been reported. The present molecular study involves a family with progressive features of CMT and deafness, originally reported by Kousseff et al. Genetic analysis of 70 individuals (31 affected, 28 unaffected, and 11 spouses) revealed linkage to markers on chromosome 17p11.2-p12, with a maximum LOD score of 9.01 for marker D17S1357 at a recombination fraction of .03. Haplotype analysis placed the CMT-deafness locus between markers D17S839 and D17S122, a approximately 0.6-Mb interval. This critical region lies within the CMT type 1A duplication region and excludes MYO15, a gene coding an unconventional myosin that causes a form of autosomal recessive deafness called DFNB3. Affected individuals from this family do not have the common 1.5-Mb duplication of CMT type 1A. Direct sequencing of the candidate peripheral myelin protein 22 (PMP22) gene detected a unique G-->C transversion in the heterozygous state in all affected individuals, at position 248 in coding exon 3, predicted to result in an Ala67Pro substitution in the second transmembrane domain of PMP22.
伴有耳聋的夏科-马里-图斯病（CMT）在基因异质性的CMT疾病组中在临床上具有独特性。尚未有关于一个常染色体显性CMT和耳聋的大家族的分子研究报道。目前的分子研究涉及一个具有CMT和耳聋进行性特征的家族，最初由库塞夫等人报道。对70名个体（31名患者、28名未患病者和11名配偶）的基因分析显示与17号染色体p11.2-p12上的标记连锁，在重组率为0.03时，标记D17S1357的最大对数优势分数为9.01。单倍型分析将CMT-耳聋基因座定位在标记D17S839和D17S122之间，这是一个约0.6兆碱基的区间。这个关键区域位于CMT1A型重复区域内，并且排除了MYO15，MYO15是一个编码非常规肌球蛋白的基因，它会导致一种常染色体隐性耳聋，称为DFNB3。来自这个家族的患病个体没有常见的CMT1A型1.5兆碱基重复。对候选外周髓磷脂蛋白22（PMP22）基因进行直接测序，在所有患病个体中检测到杂合状态下的一个独特的G→C颠换，位于编码外显子3的第248位，预计会导致PMP22第二个跨膜结构域中的丙氨酸67变为脯氨酸。
