From the Departments of Neurology (R.S., T.S., J.J.V., J.F.V., N.M., L.B.), Clinical Neurophysiology (M.J.C.), and Genetics (J.M.M.), Hospital Univesitari i Politècnic La Fe, Valencia; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (T.S., J.J.V., M.J.C., N.M., L.B.), Valencia; Departments of Medicine (T.S., J.J.V.) and Genetics (C.E.), University of Valencia; Program in Rare and Genetic Diseases (D.M.-R., F.P., C.E.), Centro de Investigación Príncipe Felipe (CIPF), Valencia; Centro de Investigación Biomédica en Red de Enfermedades Raras (D.M.-R., J.M.M., F.P., C.E.), Valencia; IBV-CSIC Associated Unit at CIPF (D.M.-R., F.P., C.E.), Valencia; and School of Medicine (F.P.), University of Castilla-La Mancha, Ciudad Real, Spain.
Neurology. 2013 Oct 29;81(18):1617-25. doi: 10.1212/WNL.0b013e3182a9f56a. Epub 2013 Sep 27.
To determine the genetic distribution and the phenotypic correlation of an extensive series of patients with Charcot-Marie-Tooth disease in a geographically well-defined Mediterranean area.
A thorough genetic screening, including most of the known genes involved in this disease, was performed and analyzed in this longitudinal descriptive study. Clinical data were analyzed and compared among the genetic subgroups.
Molecular diagnosis was accomplished in 365 of 438 patients (83.3%), with a higher success rate in demyelinating forms of the disease. The CMT1A duplication (PMP22 gene) was the most frequent genetic diagnosis (50.4%), followed by mutations in the GJB1 gene (15.3%), and in the GDAP1 gene (11.5%). Mutations in 13 other genes were identified, but were much less frequent. Sixteen novel mutations were detected and characterized phenotypically.
The relatively high frequency of GDAP1 mutations, coupled with the scarceness of MFN2 mutations (1.1%) and the high proportion of recessive inheritance (11.6%) in this series exemplify the particularity of the genetic distribution of Charcot-Marie-Tooth disease in this region.
在一个地理位置明确的地中海地区，确定广泛系列的 Charcot-Marie-Tooth 病患者的遗传分布和表型相关性。
在这项纵向描述性研究中，对大多数已知与该病相关的基因进行了彻底的遗传筛查，并进行了分析。对遗传亚组中的临床数据进行了分析和比较。
在 438 名患者中的 365 名（83.3%）完成了分子诊断，脱髓鞘形式的疾病成功率更高。CMT1A 重复（PMP22 基因）是最常见的遗传诊断（50.4%），其次是 GJB1 基因（15.3%）和 GDAP1 基因（11.5%）的突变。还发现了 13 个其他基因的突变，但频率较低。检测到并表征了 16 个新突变。
在本系列中，GDAP1 突变的相对高频，加上 MFN2 突变（1.1%）的稀少性和隐性遗传（11.6%）的高比例，说明了 Charcot-Marie-Tooth 病遗传分布的特殊性。
