Figlewicz D A, McInnis M G, Goto J, Haines J L, Warren A C, Krizus A, Khodr N, Brown R H, McKenna-Yasek D, Antonarakis S E
Centre for Research in Neuroscience, McGill University, Montreal, PQ, Canada.
J Neurol Sci. 1994 Jul;124 Suppl:90-5. doi: 10.1016/0022-510x(94)90190-2.
Amyotrophic lateral sclerosis (ALS) is a progressive, adult-onset, neurodegenerative disorder characterized by the death of large motor neurons from the cerebral cortex, brainstem, and spinal cord. The etiology of ALS remains unknown; however, approximately 10% of the cases are familial in nature. In the majority of these families, the mode of transmission is autosomal dominant. Recently, linkage of an autosomal dominant familial ALS (FALS) gene to the locus ALS1 on chromosome 21q was established. In addition, evidence was provided for genetic heterogeneity, with approximately 55% of families most likely linked to chromosome 21. The development of a number of highly informative simple sequence repeat polymorphisms in the region of linkage-21q21 through 21q22.1-has permitted us to confirm both the assignment of ALS1 to 21q and the genetic heterogeneity of FALS. In addition, we have been able to refine the mapping of ALS1, based on recombination events in two of the linked families. Flanking markers for the FALS gene are D21S213 on the centromeric side and D21S219 on the telomeric side. The candidate region is approximately 4 Mb and contains the genes copper/zinc superoxide dismutase (CuZnSOD); the fourth member of the class II cytokine receptor family (CRF2-4); and the interferon-alpha receptor (IFNAR).
肌萎缩侧索硬化症（ALS）是一种进行性、成年发病的神经退行性疾病，其特征是大脑皮层、脑干和脊髓中的大型运动神经元死亡。ALS的病因尚不清楚；然而，约10%的病例为家族性。在这些家族中的大多数，遗传方式为常染色体显性遗传。最近，常染色体显性家族性ALS（FALS）基因与21号染色体上的ALS1位点建立了连锁关系。此外，有证据表明存在遗传异质性，约55%的家族最有可能与21号染色体连锁。在连锁区域21q21至21q22.1中开发的一些高信息含量的简单序列重复多态性，使我们能够确认ALS1定位于21q以及FALS的遗传异质性。此外，基于两个连锁家族中的重组事件，我们能够完善ALS1的定位。FALS基因的侧翼标记在着丝粒侧为D21S213，在端粒侧为D21S219。候选区域约为4 Mb，包含铜/锌超氧化物歧化酶（CuZnSOD）基因、II类细胞因子受体家族的第四个成员（CRF2-4）以及干扰素-α受体（IFNAR）。
