Genotype And Hematologic Phenotype Analysis Of Hong Kongαα Thalassemia

Objectives:Analysis of genotypes and hematological phenotypes of Hong Kongααthalassemia and combined withαorβthalassemia has been rarely reported.This study aims to explore the hematologic phenotypes of Hong Kongααthalassemia and its combination with other different types of thalassemia,analyze the relationship between its genotypes and hematological phenotypes,and provide clinicians with more accurate genetic counseling and prenatal diagnosis.Methods:Patients who underwent thalassemia screening in the Affiliated Hospital of Guilin Medical College from January 2015 to December 2021 were collected for blood cell analysis,hemoglobin electrophoresis and routine thalassemia gene testing,and two-round nested PCR,multiple connection-dependent probe amplification（MLPA）and third-generation sequencing（TGS）were used to determine the type of thalassemia gene mutation in samples suspected of HKααthalassemia.Groups were based on thalassemia genotyping and third-generation sequencing.Statistical analysis was conducted with the SPSS.25.0 software.The measurement date were expressed asx±s,and the independent sample t test was utilized to compare the mean of two groups.P value<0.05 was considered statistically significant.Results:A total of 34 cases of HKααwere detected,including 20 cases of HKαα/αα,6 cases of HKαα/ααcompoundβ⁰/β^N,HKαα/ααcompoundβ⁺/β^N 2cases,HKαα/-ɑ^3.7 compositeβ⁰/β^N 1 cases,HKαα/-α^4.2 2 cases,HKαα/α^WSα1case,and HKαα/--^SEA 2 cases.Compared with the normal group,there was no significant difference in the RBC,HGB,MCV,MCH,MCHC values in the HKαα/ααgroup（P>0.05）.There was no significant difference in the values of RBC,HGB,MCV,MCH,MCHC and MCHC between HKαα/ααcompositeβ⁰thalassemia group andβ⁰ thalassemia group（P>0.05）.Individuals with HKαα/-α^4.2 and HKαα/α^WSαgenotypes showed silentα-thalassemia,while individuals with genotype HKαα/--^SEA genotype showed mildα-thalassemia.HKαα/αα,HKαα/-α^3.7 combined withβ-thalassemia displayed obvious hematologic features ofβ-thalassemia.Conclusions:1)The hematological characteristics of HKααgene carriers are the same as those of normal groups.2)When the Gap-PCR result shows-α^3.7/αα,and the patient’s hematology is normal and there are no clinical manifestations,HKαα/ααshould be vigilant.3)The hematological characteristics and genetic counseling of HKααgene mutation combined with thalassemia are similar to the corresponding thalassemia,and HKααgene mutation will not aggravate the clinical manifestations of thalassemia.4)Third-generation sequencing is a reliable,efficient and accurate method for detecting HKααthalassemia,which can be widely used in clinical practice.