Manole Andreea, Horga Alejandro, Gamez Josep, Raguer Nuria, Salvado Maria, San Millán Beatriz, Navarro Carmen, Pittmann Alan, Reilly Mary M, Houlden Henry
MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, Queen Square, London, UK.
Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
Neurogenetics. 2017 Jan;18(1):63-67. doi: 10.1007/s10048-016-0505-1. Epub 2016 Dec 22.
Biallelic mutations in the SBF1 gene have been identified in one family with demyelinating Charcot-Marie-Tooth disease (CMT4B3) and two families with axonal neuropathy and additional neurological and skeletal features. Here we describe novel sequence variants in SBF1 (c.1168C>G and c.2209_2210del) as the potential causative mutations in two siblings with severe axonal neuropathy, hearing loss, facial weakness and bulbar features. Pathogenicity of these variants is supported by co-segregation and in silico analyses and evolutionary conservation. Our findings suggest that SBF1 mutations may cause a syndromic form of autosomal recessive axonal neuropathy (AR-CMT2) in addition to CMT4B3.
在一个患有脱髓鞘型夏科-马里-图斯病(CMT4B3)的家族以及两个患有轴索性神经病并伴有其他神经和骨骼特征的家族中,已鉴定出SBF1基因的双等位基因突变。在此,我们描述了SBF1基因中的新型序列变异(c.1168C>G和c.2209_2210del),这些变异可能是导致两名患有严重轴索性神经病、听力丧失、面部无力和延髓特征的同胞发病的原因。共分离分析、计算机模拟分析以及进化保守性均支持这些变异的致病性。我们的研究结果表明,除了CMT4B3之外,SBF1基因突变可能还会导致常染色体隐性遗传性轴索性神经病(AR-CMT2)的综合征形式。