Two novel copy number variations involving the α-globin gene cluster on chromosome 16 cause thalassemia in two Chinese families

Abstract： The human α-globin gene cluster lies close to the telomere of the short arm on chromosome 16. Copy number variations (CNVs) of this region produce excessive or insufficient α-globin chains which imbalances the β-globin chains, resulting in thalassemia. However, these CNVs usually cannot be precisely defined by traditional methods. Here, we designed a technique strategy and applied it to identify two CNVs involving the α-globin gene cluster causing thalassemia in two Chinese families. A novel 282kb duplication (αααα282) was identified in family A and a novel 235kb deletion (--235) in family B. Proband A is a coinheritance of βCD41-42 and αααα282 and showed severe β-thalassemia intermedia phenotype. Proband B is a compound heterozygote of --235/αCSα genotype and was diagnosed with hemoglobin H disease. The clinical phenotypic features of the CNVs carriers were described, together with a complete picture of molecular structure of these rearrangements. Two CNVs are novel rearrangements in α-globin clusters and the αααα282 is the first to identify the exact insert position of a duplication region from the telomere on chromosome 16. The identification and characterization of these two novel CNVs demonstrates the precision and effectiveness of our strategy in analyzing the structure of unknown CNVs.