Newborn Screening for β-Thalassemia Identifies a Complex Genotype Involving a Novel β-Globin Gene Mutation (HBB:c.336dup)

Newborn screening identified a Chinese-Canadian infant who was positive for possible β-thalassemia (β-thal). Detailed family studies demonstrated that the proband was a compound heterozygote for the Chinese ^Gγ(^Aγδβ)⁰-thal deletion and a novel frameshift mutation within exon 3 (HBB:c.336dup), and heterozygous for the Southeast Asian α-thal deletion (--^SEA/αα). This case illustrates the importance of follow-up molecular testing of positive newborn screening results to confirm the diagnosis and define risks for future pregnancies.