Bort S, Sevilla T, Vílchez J J, Prieto F, Palau F
Unidad de Genética y Diagnóstico Prenatal, Hospital Universitari La Fe, Valencia.
Med Clin (Barc). 1995 May 6;104(17):648-52.
The Charcot-Marie-Tooth (CMT) disease or hereditary motor-sensitive neuropathy (HMSN) is the most frequent hereditary neuropathy. The demyelinated or type 1 form (CMT1) is the most frequently presented, commonly being of a dominant autosomic inheritance. CMT1 is heterogeneous genetically and the subjacent mutation found in most of the cases is a duplication of 1,500 kb in the CMT1A locus of chromosome 17p11.2. The aim of the present study was to determine the prevalence of CMT1A duplication in patients with CMT1 and evaluate its usefulness as a biological diagnostic marker.
The study was carried out in a group of patients with HMSN who were not related, and were distributed according to the following diagnostic categories: CMT1 (n = 49), CMT2 (n = 9), untyped CMT (n = 11) and Déjérine-Sottas (DS) disease (n = 4). To detect three alleles confirming the presence of duplication the DNA of the patients was analyzed with four polymorph markers, VAW409R3a, RM11-GT, VAW412R3HEc and EW401HE localized in the CMT1A locus.
CMT1A duplication was found in 68.7% of the patients with CMT1 and in 27.2% of untyped CMT patients. None of the individuals in the CMT2 and DS categories showed duplication. Cases pertaining to families with dominant autosomic inheritance and genetically sporadic cases were confirmed to show a high prevalence of duplication, being of 83.3% and 85.7%, respectively.
Duplication of the CMT1A locus is the most prevalent mutation found in Charcot-Marie-Tooth type 1 disease. It is a specific mutation of this disease among the different forms of hereditary motor-sensitive neuropathy. This mutation is useful as a biological marker in the diagnosis of these neuropathies.
夏科-马里-图斯病（CMT）或遗传性运动感觉神经病（HMSN）是最常见的遗传性神经病。脱髓鞘型或1型（CMT1）最为常见，通常为常染色体显性遗传。CMT1在遗传上具有异质性，大多数病例中发现的潜在突变是17号染色体p11.2区域CMT1A位点的1500 kb重复。本研究的目的是确定CMT1患者中CMT1A重复的患病率，并评估其作为生物学诊断标志物的效用。
本研究在一组无亲缘关系的HMSN患者中进行，这些患者根据以下诊断类别进行分类：CMT1（n = 49）、CMT2（n = 9）、未分型CMT（n = 11）和德热里纳-索塔斯病（DS）（n = 4）。为了检测确认重复存在的三个等位基因，使用位于CMT1A位点的四个多态性标记VAW409R3a、RM11-GT、VAW412R3HEc和EW401HE对患者的DNA进行分析。
在68.7%的CMT1患者和27.2%的未分型CMT患者中发现了CMT1A重复。CMT2和DS类别中的个体均未显示重复。与常染色体显性遗传家族相关的病例和遗传散发病例经证实重复患病率较高，分别为83.3%和85.7%。
CMT1A位点重复是1型夏科-马里-图斯病中最常见的突变。在不同形式的遗传性运动感觉神经病中，这是该疾病的一种特异性突变。这种突变作为这些神经病诊断中的生物学标志物很有用。
