罕见型β基因簇大片段纯合缺失病例的诊断及临床表型分析

Diagnosis and clinical phenotype analysis of a case with large fragment homozygous deletion of rare β gene cluster

目的基因诊断1例β基因簇大片段纯合缺失病例并分析其临床特征,为临床遗传咨询提供依据。方法应用毛细管电泳和常规地中海贫血基因检测技术检测广东惠州地区71001份外周血样本,针对可疑β基因簇大片段缺失样本加用裂缝聚合酶链反应(Gap polymerase chain reaction,Gap-PCR)技术和多重连接探针扩增技术分析其基因分型,用统计学R软件比较分析血液学特征。结果检出89例β基因簇中国型Gγ(Aγδβ)0缺失基因分型(检出率为0.13%),其中中国型Gγ(Aγδβ)0缺失杂合子70例,中国型Gγ(Aγδβ)0杂合缺失复合α地中海贫血18例,Gγ(Aγδβ)0缺失纯合子1例。建立13683例正常对照组,与杂合子携带者的6组血液学参数相比较,箱线图显示差异均具有统计学意义(P<0.05)。诊断出的1例Gγ(Aγδβ)0缺失纯合子临床表型为轻度贫血,血红蛋白电泳结果显示HbF值100%。结论惠州地区人群β基因簇大片段缺失基因型的携带率高,血液学HbF值明显升高,应重视筛查,选择性行罕见型检测,防止漏诊或误诊,指导临床遗传咨询和产前诊断。

Objective To report on a case with homozygous deletion of largeβgene cluster and its clinical characteristics.Methods A total of 71001 peripheral blood samples were subjected to capillary electrophoresis and conventional testing for common thalassemia mutations.The genotypes of suspectedβgene cluster deletions were analyzed by Gap-PCR and multiplex ligation-dependent probe amplification(MLPA).Their hematological characteristics were compared by statistical analysis R software.Results Eighty-nine cases were detected with Chinese Gγ(Aγδβ)0-deletion of theβgene cluster,which gave a detection rate of 0.13%.Among these,there were 70 Chinese Gγ(Aγδβ)0-deletion heterozygotes and 18 Chinese Gγ(Aγδβ)0-deletion heterozygotes in conjunct withαthalassemia.There were 13683 samples with normal findings.A significant difference was detected in 6 groups of hematological parameters between the heterozygous carriers(P<0.05)by box plotting.One case of Chinese Gγ(Aγδβ)0-deletion homozygote was discovered for the first time.The clinical phenotype was mild anemia.Hemoglobin electrophoresis showed that the value of HbF was 100%.Conclusion The carrier rate for large fragment deletions ofβgene cluster in Huizhou region is rather high,for which the value of HbF is significantly increased.Attention should be paid to screening and diagnosis of rare genotype to prevent missed diagnosis and/or misdiagnosis.