Genetic and phenotypic analysis of a rare asymptomatic case of a homozygous Chinese Gγ+(Aγδβ)0-thalassemia deletion in a Chinese family

Abstract Objective The clinical and hematologic features of thalassemia are due to different factors, and patients with identical genotypes may regularly exhibit variable severity. In the present work, one homozygous Chinese Gγ+(Aγδβ)0-thalassemia case with an asymptomatic phenotype, which is contrary to traditional views, was identified. Analysis of the underlying causes of this rare clinical phenotype involved accurate genetic diagnosis and detection of several genetic modifications. Methods Six members of the proband’s family were enrolled in the study. Hematological parameters and hemoglobin analysis results were recorded. A suspension-array system, multiplex gap-polymerase chain reaction (gap-PCR) and multiplex ligation-dependent probe amplification (MLPA) were used together to characterize genotypes. Sanger sequencing was utilized to examine the KLF1 gene and four primary fetal hemoglobin (Hb F)-associated single-nucleotide polymorphisms (SNPs). Results Four family members carried the Chinese Gγ+(Aγδβ)0-thalassemia mutation, and a homozygous state was ultimately diagnosed for the proband. All of the Chinese Gγ+(Aγδβ)0 mutation-positive cases were coinherited with the Southern Asian α-thalassemia deletion (– – SEA/αα). Two SNP variants, rs7776054 and rs9399137, in the HBS1L-MYB locus were detected in the proband. Conclusions Thus far, this is the first study to describe the molecular characterization of a homozygous Chinese Gγ+(Aγδβ)0-thalassemia patient who exhibits no clinical symptoms. Our findings suggest that coinheritance of α-thalassemia or HBS1L-MYB locus variants may affect the clinical severity of Chinese Gγ+(Aγδβ)0-thalassemia. We conclude that the molecular examination of genetic determinants known to be associated with clinical outcomes in Chinese Gγ+(Aγδβ)0-thalassemia should be emphasized.