1例由脐血血红蛋白电泳追溯到的罕见型新生儿β珠蛋白生成障碍性贫血基因家系分析

Gene family analysis of a rare type of neonatalβ-globin ogenesis anemia traced back by cord blood hemoglobin electrophoresis

目的对1例新生儿脐血血红蛋白电泳HbA为0,表型与基因型不符的患儿及其家系成员进行基因分析,以研究先证者及家系成员是否携带有未知突变基因,为其以后的优生遗传咨询提供依据。方法通过采集先证者家系成员外周血进行血细胞分析及血红蛋白毛细管电泳分析,采用PCR+导流杂交法检测常见型珠蛋白生成障碍性贫血基因,对表型和常见珠蛋白生成障碍性贫血基因型不相符者行基因测序。结果该家系中先证者及其母亲和姐姐检出罕见型β珠蛋白生成障碍性贫血基因CD52(GAT>GTT)位点杂合突变,先证者及其姐姐的基因型为β41-42/β52,母亲的基因型为β17/β52,父亲的基因型为β41-42/βN。结论血液学表型与基因型不符时,应进一步做罕见型基因检测,避免漏诊或误诊。该基因突变的发现,丰富了β珠蛋白生成障碍性贫血基因数据库。

Objective Gene analysis was performed on a case of neonatal with the umbilical cord blood hemoglobin electrophoresis HbA of 0,whose phenotypes were inconsistent with the genotype and the family members,in order to investigate whether the proband and family members carried the unknown mutant genes and provide basis for the eugenic genetic counseling in the future.Methods The peripheral blood of the proband family members were collected for blood cell analysis and hemoglobin capillary electrophoresis analysis.The genes of the common thalassemia were detected by the PCR+flow-through hybridization.The genome sequencing was performed for those whose phenotypes was inconsistent with the genotype of the common thalassemia.Results A rareβ-hemoglobin heterozygous mutation at CD52(GAT>GTT)was detected in the proband and the mother and sister.The genotype of the proband and the older sister wasβ41-42/β52.The maternal genotype wasβ17/β52,and the paternal genotype wasβ41-42/βN.Conclusion When the hematological phenotype does not match the genotype,the rare genotype should be further tested to avoid missed diagnosis or misdiagnosis.The discovery of this gene mutation enriches the gene database ofβ-globin ogenesis anemia.