Phenotypes of the N88S Berardinelli-Seip congenital lipodystrophy 2 mutation
Phenotypes of the N88S Berardinelli-Seip congenital lipodystrophy 2 mutation
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DOI：
10.1002/ana.20410
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发表时间：
2005-03-01
影响因子：
11.2
通讯作者：
Windpassinger, C
中科院分区：
文献类型：
--
作者：
Auer-Grumbach, M;Schlotter-Weigel, B;Windpassinger, C
最近，在常染色体显性遗传性远端遗传性运动神经病和Silver综合征中发现了Berardinelli-Seip先天性脂肪营养不良基因的两个错义突变(N88S和S90L)。我们报告了一个奥地利大家庭和两个无关的德国家庭的90名患者的N88S突变的表型结果。临床和电生理表型的差异使我们能够区分六个亚型。4.4%的患者为非穿透性疾病。20%的患者受到亚临床影响；其中一些患者只能通过病理神经传导研究才能发现。以手部肌肉受累为主要特征的远端遗传性运动神经病V型占31.1%，14.5%表现为典型的Silver综合征，伴有手部小肌萎缩和肢体痉挛。此外，20%的表型与Charcot-Marie-Tooth病相容。临床诊断为单纯或复杂遗传性痉挛截瘫的占10%。电生理检查显示轴索神经病变，但复合运动动作电位和传导阻滞也有时间离散。感觉神经传导研究很少是病理性的。我们的研究表明，Berardinelli-Seip先天性脂肪营养不良基因2的显性N88S突变导致了广泛的运动神经元疾病。
Recently, two missense mutations (N88S, S90L) in the Berardinelli-Seip congenital lipodystrophy gene have been identified in autosomal dominant distal hereditary motor neuropathy and Silver syndrome. We report the phenotypic consequences of the N88S mutation in 90 patients of 1 large Austrian family and two unrelated German families. Variation in the clinical and electrophysiological phenotype enabled us to distinguish six subtypes. In 4.4%, the disorder was not penetrant. Twenty percent of the patients were subclinically affected; some of these patients could only be detected by pathological nerve conduction studies. A distal hereditary motor neuropathy type V phenotype characterized by predominant hand muscle involvement was found in 31.1%, whereas 14.5% showed typical Silver syndrome with amyotrophy of the small hand muscles and spasticity of the lower extremities. Moreover, the phenotype present in 20% was compatible with Charcot-Marie-Tooth disease. In 10%, the clinical diagnosis of pure or complicated hereditary spastic paraparesis was made. Electrophysiological studies showed an axonal neuropathy but also chronodispersion of compound motor action potentials and conduction blocks. Sensory nerve conduction studies were rarely pathological. Our study indicates that the dominant N88S mutation in the Berardinelli-Seip congenital lipodystrophy gene 2 leads to a broad spectrum of motor neuron disorders.