The genotype and phenotype analysis in 3 cases with the rare genotype of HBB:c.316-146T > G.

Objectives: To explore the genotypic and phenotypic characteristics of HBB: c.316-146T > G carriers in China.

Methods: The blood routine parameters and hemoglobin electrophoresis data of carriers were analyzed using PCR combined with reverse dot blot (RDB), gap-PCR, and DNA sequencing.

Results: The blood routine parameters of all these three cases were MCV < 82fl and MCH < 27pg, and hemoglobin electrophoresis showed HbA₂ ≥ 4.60%. Genetic testing results: two cases were heterozygous mutations of HBB:c.316-146T > G, the other one was heterozygous mutation of HBB:c.316-146T > G combined with -^SEA deletion.

Conclusion: The hematological phenotype of HBB:c.316-146T > G mutation carriers is similar to that of common β⁺ heterozygous mutations, presenting with hypochromic, microcytic red cell indices. If the hematological phenotype does not match the results of genetic testing, further detection techniques such as Sanger sequencing, MLPA, next-generation sequencing (NGS), etc. are required to avoid missing rare or novel mutation types.