title: 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 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.
authors.affiliation: Hemoglobinopathy Reference Laboratory, Children's Hospital & Research Center Oakland, Oakland, California, USA.
authors.forename: Jialing
authors.initials: J
authors.lastname: Cui
authors.forename: Mahin
authors.initials: M
authors.lastname: Azimi
authors.forename: Christoph
authors.initials: C
authors.lastname: Baysdorfer
authors.forename: Elliott P
authors.initials: EP
authors.lastname: Vichinsky
authors.forename: Carolyn C
authors.initials: CC
authors.lastname: Hoppe
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family; D060885:Multiplex Polymerase Chain Reaction; D010641:Phenotype; D044469:Racial Groups; D017384:Sequence Deletion; D012720:Severity of Illness Index; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology
chemical_list: D055544:beta-Globins