Application of Multiplex Ligation-Dependent Probe Amplification to Screen for β-Globin Cluster Deletions: Detection of Two Novel Deletions in a Multi Ethnic Population

Abstract

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 β0, 3.5 kb Thai β0, 118 kb Filipino β0, 11.8 kb Black (δβ)0, 13.4 kb Sicilian (δβ)0, 35.8 kb Black (Aγδβ)0, Hb Lepore-Boston-Washington (Hb LBW) and HPFH-2 deletions, and two novel deletions, a 61.7 kb Pakistani β0 deletion and an (Aγδβ)0 deletion, were identified in 15 cases. Detection of both known and unknown deletional Hb disorders provides for appropriate clinical management and genetic counseling.