Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA/A)

X-linked sideroblastic anemia and ataxia (XLSA/A) is a recessive disorder characterized by an infantile to early childhood onset of non-progressive cerebellar ataxia and mild anemia with hypochromia and microcytosis. A gene encoding an ATP-binding cassette (ABC) transporter was mapped to Xq13, a region previously shown by linkage analysis to harbor the XLSA/A gene. This gene, ABC7, is an ortholog of the yeast ATM1 gene whose product localizes to the mitochondrial inner membrane and is involved in iron homeostasis. The full-length ABC7 cDNA was cloned and the entire coding region screened for mutations in a kindred in which five male members manifested XLSA/A. An I400M variant was identified in a predicted transmembrane segment of the ABC7 gene in patients with XLSA/A. The mutation was shown to segregate with the disease in the family and was not detected in at least 600 chromosomes of general population controls. Introduction of the corresponding mutation into the Saccharomyces cerevisiae ATM1 gene resulted in a partial loss of function of the yeast Atm1 protein. In addition, the human wild-type ABC7 protein was able to complement ATM1 deletion in yeast. These data indicate that ABC7 is the causal gene of XLSA/A and that XLSA/A is a mitochondrial disease caused by a mutation in the nuclear genome.     

脊髓小脑共济性失调2型家系永生细胞株的建立及遗传稳定性检测

目的 建立伴帕金森氏病症状的脊髓小脑共济性失调2型家系永生细胞株,提供永久性的实验研究材料.方法 采用EB病毒加入环胞霉素A的转化细胞技术,建立了该家系的永生细胞株.并检测传代细胞与家系血液中的微卫星标记有无改变,确定细胞株的遗传稳定性.结果 成功建立此家系25株永生细胞株,所检测的微卫星位点未发生变化.结论 所建永生细胞株染色体核型检测无异常,转化细胞株与血液中的微卫星的遗传稳定性无差异.