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Anti-Lepore hemoglobins (Hbs) are rare βδ fusion variants that arise from non homologous crossover during meiosis. Using multiplex ligation-dependent probe amplification (MLPA), we identified a novel anti-Lepore Hb in an individual with an ambiguous Hb variant detected on routine screening by electrophoresis and high performance liquid chromatography (HPLC). The results of MLPA revealed duplication of β and δ gene segments. Resolution of the rearrangement by DNA sequencing confirmed a novel anti-Lepore Hb, molecularly distinct from Hb P-Nilotic, which we have named anti-Lepore Hb CHORI (Children's Hospital Oakland Research Institute) (β(through IVS-I-57)/δ(from IVS-I-101)).

Hereditary persistence of fetal hemoglobin (HPFH) and δβ-thalassemia (δβ-thal) are heterogeneous disorders caused by deletions within the β-globin gene cluster. When combined with other β-thal mutations or structural hemoglobin (Hb) variants, these deletions give rise to clinical phenotypes ranging from an asymptomatic condition to β-thal major (β-TM). Overlap in hematological parameters and variability in expression of Hbs A2 and F make molecular testing necessary to distinguish clinically relevant deletions. Multiplex ligation-dependent probe amplification (MLPA) was used to screen for β-globin gene cluster deletions in 49 unresolved samples referred for a suspected β-thal anomaly. The 1.39 kb Black β(0), 3.5 kb Thai β(0), 118 kb Filipino β(0), 11.8 kb Black (δβ)(0), 13.4 kb Sicilian (δβ)(0), 35.8 kb Black ((A)γδβ)0, Hb Lepore-Boston-Washington (Hb LBW) and HPFH-2 deletions, and two novel deletions, a 61.7 kb Pakistani β(0) deletion and an ((A)γδβ)(0) deletion, were identified in 15 cases. Detection of both known and unknown deletional Hb disorders provides for appropriate clinical management and genetic counseling.

Anti-Lepore hemoglobins (Hbs) are rare βδ fusion variants that arise from non homologous crossover during meiosis. We describe the application of multiplex ligation-dependent probe amplification (MLPA) to test for a suspected anti-Lepore Hb in an individual with an ambiguous Hb variant detected on routine screening by electrophoresis and high performance liquid chromatography (HPLC). The results of MLPA revealed duplication of β and δ gene segments consistent with an anti-Lepore βδ fusion gene. Resolution of the hybrid gene by DNA sequencing identified the variant as Hb P-Nilotic (β31-δ50) HBB/HBD hybrid; HBB through 22; HBD from 50 (NG_000007.3:g.63290_70702dup). Multiples ligation-dependent probe amplification allows for rapid detection of hybrid globin variants caused by duplications in the β-globin gene locus.