Identification of a novel 145 kb deletion (Guigang deletion, -Guigang) in the alpha-globin gene cluster from a Chinese newborn using third-generation sequencing

Objective To describe a novel alpha-thalassemiadeletion identified from a newborn by third-generation sequencing (TGS). Case report The proband, a newborn subject to neonatal capillary electrophoresis (CE) screening, exhibited suspected alpha(0)-thalassemia carrier status (Hb Bart's 3.0%). Notably, both parents had negative results on thalassemia screening during pregnancy. Multiplex ligation-dependent probe amplification (MLPA) presented a deletion between probes 364nt and 472 nt that extended from the HBZ gene to the downstream region of the RGS11 gene. Subsequently, TGS determined the approximated break position of this deletion, indicating a length exceeding 145 kb (chr16:127,815-273,190 del 145376 bp). Sanger sequencing validated the upstream and downstream breakpoints of this deletion. Only maternal data were available for pedigree analysis, with the father's sample lacking. MLPA showed no deletion in the mother, suggesting possible paternal inheritance. The deletion was named Guigang deletion (--(Guigang)) after the proband's city of origin, Guigang. Conclusions We reported a novel alpha-thalassemiadeletion and provided insights into the hematological phenotype and molecular analysis. These findings have implications for genetic counseling and prenatal diagnosis.