Charcot-Marie-Tooth disease: frequency of genetic subtypes in a Southern Italy population
Charcot-Marie-Tooth disease: frequency of genetic subtypes in a Southern Italy population
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DOI：
10.1111/jns.12092
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发表时间：
2014-12-01
影响因子：
3.8
通讯作者：
Santoro, Lucio
中科院分区：
文献类型：
--
作者：
Manganelli, Fiore;Tozza, Stefano;Santoro, Lucio
本研究的目的是评估腓骨肌萎缩症（CMT）在坎帕尼亚，意大利南部地区的遗传分布。我们分析了197例索引病例的队列，并报告了整个CMT人群和每个电生理组（CMT 1，CMT 2和遗传性神经病与压力麻痹易感性[HNPP]）以及家族性和孤立性CMT病例的突变类型和频率。在148例患者（75.1%）中实现了基因诊断，HNPP和CMT 1的成功率高于CMT 2。只有四个基因（PMP 22，GJB 1，MPZ和GDAP 1）占所有遗传学确诊的CMT病例的92%。在CMT 1中，PMP 22重复突变是最常见的突变，其次是家族性MPZ和孤立病例中的SH 3 TC 2。在CMT 2中，GJB 1是最常见的突变基因，并且GJB 1与GDAP 1占遗传定义的CMT 2患者的近3/4。在家族性病例中，GJB 1基因频率居第一位，在孤立病例中，GDAP 1基因频率居第一位。在HNPP中，大多数患者携带PMP 22基因缺失。我们的数据的新奇是SH 3 TC 2和GDAP 1突变在脱髓鞘和轴突形式中的频率相对较高。这些流行病学数据可以帮助我们的患者群体进行面板设计。
The objective of this study is to assess the genetic distribution of Charcot-Marie-Tooth (CMT) disease in Campania, a region of Southern Italy. We analyzed a cohort of 197 index cases and reported the type and frequency of mutations for the whole CMT population and for each electrophysiological group (CMT1, CMT2, and hereditary neuropathy with susceptibility to pressure palsies [HNPP]) and for familial and isolated CMT cases. Genetic diagnosis was achieved in 148 patients (75.1%) with a higher success rate in HNPP and CMT1 than CMT2. Only four genes (PMP22, GJB1, MPZ, and GDAP1) accounted for 92% of all genetically confirmed CMT cases. In CMT1, PMP22 duplication was the most common mutation while the second gene in order of frequency was MPZ in familial and SH3TC2 in isolated cases. In CMT2, GJB1 was the most frequent mutated gene and GJB1 with GDAP1 accounted for almost 3/4 of genetically defined CMT2 patients. The first gene in order of frequency was GJB1 in familial and GDAP1 in isolated cases. In HNPP, the majority of patients harbored the PMP22 gene deletion. The novelty of our data is the relatively high frequency of SH3TC2 and GDAP1 mutations in demyelinating and axonal forms, respectively. These epidemiological data can help in panel design for our patients' population.