A Novel 165 Kb Duplication Involving the α-Globin Gene Cluster Is Identified by Low-Pass Whole Genome Sequencing in a Chinese Thalassemia Intermedia Patient

Copy number variations (CNVs) involving the alpha-globin gene cluster can lead to an imbalance in the proportion of alpha- and beta-globin chains and consequently cause clinical symptoms of beta-thalassemia. In our case, a 6-year-old boy, clinically diagnosed with beta thalassemia intermedia, was admitted for further genetic diagnosis with his family. Targeted sequencing and third generation sequencing (TGS) were used to detect the possible variants of the thalassemia genes. Low-pass whole genome sequencing (lpWGS) was conducted to specify the exact location of relevant CNVs across the genome, which was then validated by multiplex ligation-dependent probe amplification.The results revealed that the patient had a heterozygous beta 0 mutation of Codon17 (A > T) and a full duplication of the alpha-globin gene cluster, inherited from his mother and father, respectively. Besides, a novel point mutation within the 5 ' untranslated region of beta-Globin (HBB: c. -175 (G > A) was only detected in the patient. This study suggests that lpWGS seems a powerful alternative to detect large CNVs related to thalassemia with second intention for more information of the breakpoints and a simultaneous genome-scale detection of other pathogenic CNVs.