Beutler E, West C, Britton H A, Harris J, Forman L
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Blood Cells Mol Dis. 1997 Dec;23(3):402-9. doi: 10.1006/bcmd.1997.0157.
Five unrelated patients with hereditary glucosephosphate isomerase (GPI) deficiency resulting in nonspherocytic hemolytic anemia were studied. Three new mutations were found in the coding region of the GPI gene: two patients were heterozygous for 223 A-->G (R75G) and 898 G-->C(R300P), respectively and one was homozygous for 1415G-->A(R472H). Surprisingly, 2 previously reported mutations, 286 C-->T and 1039 C-->T, were found in 2 and 3 patients respectively. Until now only 4 of 18 GPI mutations had been found more than once in unrelated patients and these 4 in only 2 patients each. Eleven of the 20 known point mutations have occurred at CpG "hot spots" and the 286 C-->T and 1039 C-->T are among these. The 489 G/A polymorphism in the GPI coding region was used to demonstrate unequivocally that the 1039 C-->T mutation occurred in both haplotypes and therefore probably originated more than once. Because no common GPI mutation has been found we suggest that heterozygosity for GPI confers little if any selective advantage.
对5名患有遗传性葡萄糖磷酸异构酶（GPI）缺乏症并导致非球形红细胞溶血性贫血的非亲属患者进行了研究。在GPI基因的编码区发现了3个新突变：2名患者分别为223 A→G（R75G）和898 G→C（R300P）的杂合子，1名患者为1415G→A（R472H）的纯合子。令人惊讶的是，在2名和3名患者中分别发现了2个先前报道的突变，即286 C→T和1039 C→T。到目前为止，在非亲属患者中，18个GPI突变中只有4个被不止一次发现，且这4个突变每次仅在2名患者中出现。已知的20个点突变中有11个发生在CpG“热点”，286 C→T和1039 C→T就在其中。利用GPI编码区的489 G/A多态性明确证明，1039 C→T突变存在于两种单倍型中，因此可能不止一次发生。由于未发现常见的GPI突变，我们认为GPI杂合性几乎没有（如果有的话）赋予任何选择优势。
