Catalog of 73 novel variants in thalassemia: discoveries and insights

Thalassemia is a genetic blood disorder caused by disrupted hemoglobin synthesis, posing significant public health challenges. This study aims to expand the identification of novel thalassemia variants in a large cohort from pre-marriage screenings in Ganzhou, Southern Jiangxi, China. Data from 229 246 individuals screened through Next-Generation Sequencing (NGS) from 2019 to 2022 led to the identification of 180 participants with novel variants, marking the first large-scale documentation of such variations in the population. Among them, 51.1% were male with a mean age of 27 years, and the frequency of novel thalassemia variants was 0.079%. We uncovered 180 novel variants, including 68 α-thalassemia variants across 33 types (0.0297% frequency) and 112 β-thalassemia variants belonging to 40 unique types (0.0489% frequency). The most common α-thalassemia genotype was HBA1:c.95 + 9C > T at 17.65%, while HBB:c.-180G > C was most prevalent among β-thalassemia variants at 23.21%. Ten novel α-thalassemia variants were linked to mild α-thalassemia, and clinical phenotypes were documented for 21 complex genotypes. This study catalogues 73 novel variants and highlights the genetic diversity of thalassemia, informing future preventive strategies.