Peeters Kristien, Chamova Teodora, Jordanova Albena
1 Molecular Neurogenomics Group, Department of Molecular Genetics, VIB, University of Antwerp, Antwerpen 2610, Belgium 2 Neurogenetics Laboratory, Institute Born-Bunge, University of Antwerp, Antwerpen 2610, Belgium
3 Department of Neurology, Medical University-Sofia, Sofia 1000, Bulgaria
Brain. 2014 Nov;137(Pt 11):2879-96. doi: 10.1093/brain/awu169. Epub 2014 Jun 25.
Hereditary spinal muscular atrophy is a motor neuron disorder characterized by muscle weakness and atrophy due to degeneration of the anterior horn cells of the spinal cord. Initially, the disease was considered purely as an autosomal recessive condition caused by loss-of-function SMN1 mutations on 5q13. Recent developments in next generation sequencing technologies, however, have unveiled a growing number of clinical conditions designated as non-5q forms of spinal muscular atrophy. At present, 16 different genes and one unresolved locus are associated with proximal non-5q forms, having high phenotypic variability and diverse inheritance patterns. This review provides an overview of the current knowledge regarding the phenotypes, causative genes, and disease mechanisms associated with proximal SMN1-negative spinal muscular atrophies. We describe the molecular and cellular functions enriched among causative genes, and discuss the challenges in the post-genomics era of spinal muscular atrophy research.
遗传性脊髓性肌萎缩症是一种运动神经元疾病，其特征是由于脊髓前角细胞变性导致肌肉无力和萎缩。最初，该疾病被单纯认为是由5号染色体长臂13区（5q13）上功能缺失的运动神经元存活基因1（SMN1）突变引起的常染色体隐性疾病。然而，新一代测序技术的最新进展揭示了越来越多被称为非5q型脊髓性肌萎缩症的临床病症。目前，16个不同的基因和一个未解决的基因座与近端非5q型相关，具有高度的表型变异性和多样的遗传模式。本综述概述了目前关于近端SMN1阴性脊髓性肌萎缩症的表型、致病基因和疾病机制的知识。我们描述了致病基因中富集的分子和细胞功能，并讨论了脊髓性肌萎缩症研究的后基因组时代所面临的挑战。
