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

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.