中国罕见的移码突变型β珠蛋白生成障碍性贫血家系调查

Family Investigation on Rare Frameshift Mutant β Thalassemia in China

目的 鉴定一位育龄妇女所携带的在中国人中罕见的β珠蛋白生成障碍性贫血基因突变并对其家系进行研究.方法 将先证者及其他3位家系成员（父亲、母亲与丈夫）一起作为调查分析对象.血液学表型分析采用常规红细胞指数及高效液相色谱技术（HPLC）;α与β珠蛋白生成障碍性贫血常规基因检测分别采用Gap-PCR和反向点杂交法（RDB）.另外对常规基因检测不能确诊的β珠蛋白生成障碍性贫血基因突变进行β珠蛋白基因序列测定.结果 先证者及其父亲具有典型的β珠蛋白生成障碍性贫血血液学表型,RDB法未检测出已知的β珠蛋白生成障碍性贫血突变类型,测序显示这两位家系成员的β珠蛋白基因共缺失CD89-CD92全部的密码子和CD93第1与第2位的核苷酸（-AGTGAGCTG-CACTG,-14bp）,并发生了移码突变,使CD89位上提前出现终止密码子TGA;先证者丈夫基因型为CD41-42（-TCTT）/N.结论 CD89-93（-14bp）移码突变在中国人群中属于比较罕见的β珠蛋白生成障碍性贫血类型,其在β珠蛋白生成障碍性贫血高风险家庭中的检出,对β珠蛋白生成障碍性贫血的产前诊断工作有参考价值.

Objective To identify a rare β thalassemia mutation in a Chinese woman at reproductive age and study her pedi-gree. Methods The proband and the other three family members （father,mother and husband） were together included as in-vestigation object. Standard hematological technique and HPLC were used to analysis the phenotype. Gap-PCR and reversedot blot（RDB）techniques were used to analyze the known thalassemia mutation of a-globin and β-globin gene, respectively. β-globin DNA sequencing was used when the regular methods could not confirm. Results The proband and her father presen-ted a typical thalassemia phenotype, but no known β thalassemia mutations were found in them by RDB. Sequence analysisrevealed these two samples carried a 14 nucleotides deletion （-AGTGAGCTGCACTG,-14bp） of all codons from CD89 toCD92 and both the first and the second nucleotides at CD93 in the globin gene,and this mutation shifted the reading frameof the globin,resulting in the creation of a stop codon （TGA） at CD 89. The globin genotype of the proband＇s husbandwas CD41-42（-TCTT）/N. Conclusion CD89-93 （-14bp） frameshift mutation is a rare β thalassemia phenotype in Chinesepopulation,and its report in a high-risk βthalassemia family has some reference value for prenatal diagnostic work of βthalassemia.