The 1357 bp deletion in β-thalassemia: molecular profiling and hematological characterization in a Guangxi cohort

The 1357 bp deletion is a rare type of β-thalassemia, and the literature on its characterization is very limited. This study aimed to conduct molecular diagnosis and clinical analysis of a 1357 bp deletion in the Guangxi cohort.

This was a retrospective study in which all samples with Hb F > 5% and/or Hb A₂ > 3.5% suspected of β-thalassemia/hereditary persistence of fetal hemoglobin (HPFH) were enrolled in the study from 2016 to 2024. Routine genetic analysis was detected 24 common α- and β-thalassemia variants. For unresolved cases, Sanger sequencing was applied to identify novel variants in HBB and HBG genes. Additionally, Gap-PCR with specific primers and multiplex ligation-dependent probe amplification (MLPA) were utilized to screen for potential deletions. Finally, third-generation sequencing (TGS) was implemented to confirm duplicated genomic segments.

A cohort of 65 individuals was analyzed, revealing heterozygous β-thalassemia/HPFH/δβ-thalassemia in 83.1% (54/65) of cases. Among these, 37.0% (20/54) carried the 1357 bp deletion, 46.3% (25/54) exhibited Chinese ^Gγ(Aγδβ)⁰-thalassemia, and 16.7% (9/54) displayed SEA-HPFH. Genotypic analysis of the 1357 bp deletion showed four distinct profiles: simple heterozygotes (75%, 15/20), compound heterozygotes with α-thalassemia (15%, 3/20), compound heterozygotes with β-thalassemia (5%, 1/20), and compound heterozygotes with HPFH (5%, 1/20). Hematologically, the 1357 bp deletion presented with microcytic, hypochromic erythrocytes alongside elevated Hb A₂ and Hb F levels. Geographically, Beihai City (70%, 14/20) demonstrated the highest prevalence of this deletion within the Guangxi region.

This study provides the first comprehensive characterization of the 1357 bp deletion, delineating its hematological profiles, molecular features, and region-specific prevalence patterns within the Guangxi Region. Accurate identification of molecular defects through phenotype-genotype correlation is important for genetic counseling and prenatal diagnosis.