Plummer N W, Galt J, Jones J M, Burgess D L, Sprunger L K, Kohrman D C, Meisler M H
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, 48109-0618, USA.
Genomics. 1998 Dec 1;54(2):287-96. doi: 10.1006/geno.1998.5550.
The voltage-gated sodium channel SCN8A is associated with inherited neurological disorders in the mouse that include ataxia, dystonia, severe muscle weakness, and paralysis. We report the complete coding sequence and exon organization of the human SCN8A gene. The predicted 1980 amino acid residues are distributed among 28 exons, including two pairs of alternatively spliced exons. The SCN8A protein is evolutionarily conserved, with 98.5% amino acid sequence identity between human and mouse. Consensus sites for phosphorylation of serine/threonine and tyrosine residues are present in cyoplasmic loop domains. The polymorphic (CA)n microsatellite marker D12S2211, with PIC = 0.68, was isolated from intron 10C of SCN8A. Single nucleotide polymorphisms in intron 19 and exon 22 were also identified. We localized SCN8A to chromosome band 12q13.1 by physical mapping on a YAC contig. The cDNA clone CSC-1 was reported by others to be a cardiac-specific sodium channel, but sequence comparison demonstrates that it is derived from exon 24 of human SCN8A. The genetic information described here will be useful in evaluating SCN8A as a candidate gene for human neurological disease.
电压门控钠通道SCN8A与小鼠的遗传性神经疾病相关，这些疾病包括共济失调、肌张力障碍、严重肌无力和瘫痪。我们报道了人类SCN8A基因的完整编码序列和外显子组织。预测的1980个氨基酸残基分布在28个外显子中，包括两对可变剪接外显子。SCN8A蛋白在进化上是保守的，人与小鼠之间的氨基酸序列同一性为98.5%。丝氨酸/苏氨酸和酪氨酸残基磷酸化的共有位点存在于细胞质环结构域中。从SCN8A的第10C内含子中分离出多态性（CA）n微卫星标记D12S2211，其PIC = 0.68。还鉴定了第19内含子和第22外显子中的单核苷酸多态性。我们通过在YAC重叠群上进行物理作图，将SCN8A定位到染色体带12q13.1。其他人报道cDNA克隆CSC-1是一种心脏特异性钠通道，但序列比较表明它来源于人类SCN8A的第24外显子。这里描述的遗传信息将有助于评估SCN8A作为人类神经疾病候选基因的可能性。
