Clinical, electrophysiological and morphological findings of Charcot-Marie-Tooth neuropathy with vocal cord palsy and mutations in the GDAP1 gene
Clinical, electrophysiological and morphological findings of Charcot-Marie-Tooth neuropathy with vocal cord palsy and mutations in the GDAP1 gene
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DOI：
10.1093/brain/awg202
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发表时间：
2003-09-01
期刊：
影响因子：
14.5
通讯作者：
Vílchez, JJ
中科院分区：
文献类型：
--
作者：
Sevilla, T;Cuesta, A;Vílchez, JJ
研究人员对三个患有常染色体隐性遗传性严重遗传性运动和感觉神经病的西班牙家庭进行了研究，这些家族在夏科-玛丽-图思 (CMT) 4A 型基因座中显示神经节苷脂诱导分化相关蛋白 1 (GDAP1) 基因发生突变。这种疾病始于新生儿期或婴儿早期，表现为双脚无力和消瘦，随后手部受累，导致严重残疾。到了十几岁的时候，一些患者出现声音嘶哑和声带麻痹。在许多情况下，由于远端萎缩导致肌肉反应缺失，因此无法测量周围运动神经传导速度（MNCV）。然而，近端肌肉的潜伏期在正常范围内；在可以测量的情况下，中值 MNCV >40 m/s。两名患者的腓肠神经活检显示有髓鞘纤维明显减少、再生簇和轴突萎缩的迹象。此外，还发现了一小部分细有髓纤维和形成洋葱鳞茎结构的雪旺细胞增殖。无髓纤维数量显着增加。这些发现表明轴突变性占主导地位，并伴有一些脱髓鞘特征。这些西班牙家庭与一些突尼斯家庭共享严重的 CMT 临床表型，这些家庭也出现了 GDAP1 基因突变，并且 CMT4A 基因座最初归属于该基因。然而，我们的家族在是否存在喉部受累和 MNCV 值方面存在差异，并且病理特征更符合 CMT2 型。 GDAP1基因突变在不同表型下表达的可能性是一个有待解决的问题。
Three Spanish families with an autosomal recessive severe hereditary motor and sensory neuropathy, showing mutations in the ganglioside-induced-differentiation-associated protein 1 (GDAP1) gene in the Charcot-Marie-Tooth (CMT) type 4A locus were studied. The disorder started in the neonatal period or early infancy with weakness and wasting of the feet and, subsequently, involvement of the hands, causing severe disability. By the late teens, some patients developed a hoarse voice and vocal cord paresis. Peripheral motor nerve conduction velocity (MNCV) could not be measured in many cases because of the absence of muscle response due to distal atrophy. However, latencies to proximal muscles were in the normal range; median MNCV was >40 m/s in those cases in which it could be measured. Sural nerve biopsy from two patients showed a pronounced depletion of myelinated fibres, regenerative clusters and signs of axonal atrophy. Additionally, a small proportion of thin myelinated fibres and proliferation of Schwann cells forming onion bulb structures were also found. Unmyelinated fibre population was markedly increased. These findings are indicative of a predominant axonal degeneration with some demyelinating features. These Spanish families share in the severe CMT clinical phenotype with some Tunisian families who also presented mutations in the GDAP1 gene and to which the CMT4A locus was originally assigned. However, our families differ in the presence of laryngeal involvement and values of MNCV and pathological features are more in line with CMT2 type. The possibility that GDAP1 gene mutations could be expressed under different phenotypes is a question to be resolved.