Gemelli Chiara, Geroldi Alessandro, Massucco Sara, Trevisan Lucia, Callegari Ilaria, Marinelli Lucio, Ursino Giulia, Hamedani Mehrnaz, Mennella Giulia, Stara Silvia, Maggi Giovanni, Mori Laura, Schenone Cristina, Gotta Fabio, Patrone Serena, Mammi Alessia, Origone Paola, Prada Valeria, Nobbio Lucilla, Mandich Paola, Schenone Angelo, Bellone Emilia, Grandis Marina
Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences (DINOGMI), University of Genova, 16126 Genova, Italy.
IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.
Life (Basel). 2022 Mar 10;12(3):402. doi: 10.3390/life12030402.
Charcot-Marie-Tooth (CMT) disease is the most commonly inherited neurological disorder. This study includes patients affected by CMT during regular follow-ups at the CMT clinic in Genova, a neuromuscular university center in the northwest of Italy, with the aim of describing the genetic distribution of CMT subtypes in our cohort and reporting a peculiar phenotype. Since 2004, 585 patients (447 index cases) have been evaluated at our center, 64.9% of whom have a demyelinating neuropathy and 35.1% of whom have an axonal neuropathy. A genetic diagnosis was achieved in 66% of all patients, with the following distribution: CMT1A (48%), HNPP (14%), CMT1X (13%), CMT2A (5%), and P0-related neuropathies (7%), accounting all together for 87% of all the molecularly defined neuropathies. Interestingly, we observe a peculiar phenotype with initial exclusive lower limb involvement as well as lower limb involvement that is maintained over time, which we have defined as a "strictly length-dependent" phenotype. Most patients with this clinical presentation shared variants in either or genes. The identification of distinctive phenotypes such as this one may help to address genetic diagnosis. In conclusion, we describe our diagnostic experiences as a multidisciplinary outpatient clinic, combining a gene-by-gene approach or targeted gene panels based on clinical presentation.
夏科-马里-图斯（CMT）病是最常见的遗传性神经疾病。本研究纳入了在意大利西北部的神经肌肉大学中心热那亚的CMT诊所定期随访期间受CMT影响的患者，目的是描述我们队列中CMT亚型的基因分布，并报告一种特殊的表型。自2004年以来，我们中心评估了585例患者（447例索引病例），其中64.9%患有脱髓鞘性神经病，35.1%患有轴索性神经病。66%的患者获得了基因诊断，分布如下：CMT1A（48%）、遗传性压迫易感性神经病（HNPP，14%）、CMT1X（13%）、CMT2A（5%）和P0相关神经病（7%），这些共占所有分子定义的神经病的87%。有趣的是，我们观察到一种特殊的表型，最初仅累及下肢，且随着时间推移下肢受累持续存在，我们将其定义为“严格长度依赖性”表型。大多数有这种临床表现的患者在 或 基因中存在共同变异。识别这样独特的表型可能有助于进行基因诊断。总之，我们描述了作为一个多学科门诊诊所的诊断经验，结合了逐个基因方法或基于临床表现的靶向基因panel。
