Harkness M, Harkness D R, Kutlar F, Kutlar A, Wilson J B, Webber B B, Codrington J F, Huisman T H
Department of Pediatrics, University of Wisconsin, Madison 53792.
Hemoglobin. 1990;14(5):479-89. doi: 10.3109/03630269009005801.
A severe hemolytic anemia with microcytosis and hypochromia was present in a young adopted Indian patient. Reversed phase high performance liquid chromatographic methodology and heat stability tests detected an unstable alpha chain which was present in 3 to 5% of the total hemoglobin. A larger quantity of the alpha X chain was obtained by preparative reversed phase high performance liquid chromatography. Structural analyses identified an Ala----Pro replacement at position 130 of the alpha chain. The instability of the variant, named Hb Sun Prairie, is comparable to that of Hb Bibba [alpha 136 (H19)Leu----Pro]. Gene mapping failed to detect an alpha-thalassemia deletion (alpha alpha/alpha alpha), while dot-blot analysis of amplified DNA with synthetic probes localized a G----C mutation in codon 130 (resulting in the Ala----Pro mutation) of the alpha 2-globin genes of both chromosomes. These results suggest a homozygosity for the G----C mutation and the condition alpha 2(G----C)alpha 1/alpha 2(G----C)alpha 1 adequately explains the rather severe clinical status of this child, including the marked microcytosis and hypochromia. Unfortunately, family studies to exclude the presence of a large deletion involving all zeta- and alpha-globin genes were not possible.
一名年轻的领养印度患者患有严重的溶血性贫血，伴有小红细胞症和低色素血症。反相高效液相色谱法和热稳定性测试检测到一条不稳定的α链，其占总血红蛋白的3%至5%。通过制备型反相高效液相色谱法获得了更多数量的αX链。结构分析确定α链第130位存在丙氨酸到脯氨酸的替换。这种名为Hb Sun Prairie的变异体的不稳定性与Hb Bibba [α136 (H19)Leu→Pro]相当。基因定位未能检测到α地中海贫血缺失（αα/αα），而用合成探针进行的扩增DNA斑点印迹分析在两条染色体的α2 -珠蛋白基因的第130密码子（导致丙氨酸到脯氨酸的突变）中定位到一个G→C突变。这些结果表明该G→C突变为纯合子，α2(G→C)α1/α2(G→C)α1这种情况充分解释了该患儿相当严重的临床状况，包括明显的小红细胞症和低色素血症。不幸的是，无法进行家族研究以排除涉及所有ζ和α珠蛋白基因的大片段缺失的存在。
