title: Detection of germline rearrangements in patients with α- and β-thalassemia using high resolution array CGH.
abstract: Approximately 80% of α-thalassemia mutations are deletions in the α-globin cluster on chromosome 16 and about 10% of β-thalassemia mutations are deletions in the β-globin gene cluster on chromosome 11. Larger deletions involving the β-globin gene cluster lead to (δβ)-, (γδβ)-, (εγδβ)-thalassemia, or hereditary persistence of fetal hemoglobin (HPFH). Array comparative genomic hybridization (CGH) was applied to screen for deletions in the α- and β-globin gene clusters not detected by routine gap-PCR. In total, in 13 patients with hypochromia and inclusion bodies (IBs) the α-globin gene cluster was analyzed and in 13 patients with increased fetal hemoglobin levels with or without hypochromia the β-globin gene cluster was examined. All samples were subsequently investigated by multiplex ligation-dependent probe amplification (MLPA). In 9 out of 13 patients deletions of the α-globin gene cluster were identified; 5 of these deletions remove the entire α-globin cluster and extend to the telomere. Additional sequencing of the remaining 4 patients revealed polyadenylation mutation in 1 of them. 7 deletions were identified in the β-globin gene cluster in 13 patients. Additional sequencing of the remaining 6 patients revealed mutations in one of the γ-globin gene promoters in 3 of them and a KLF1-mutation in 1 of them. Array CGH is a reliable method to screen for deletions in thalassemia and hemoglobinopathy. The method offers the advantage of a high resolution with the possibility to characterize breakpoints on sequence level.
authors.affiliation: Center of Laboratory Medicine, Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland.
authors.forename: Ariane
authors.initials: A
authors.lastname: Blattner
authors.forename: Saskia
authors.initials: S
authors.lastname: Brunner-Agten
authors.forename: Katja
authors.initials: K
authors.lastname: Ludin
authors.forename: Martin
authors.initials: M
authors.lastname: Hergersberg
authors.forename: Roberto
authors.initials: R
authors.lastname: Herklotz
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Huber
authors.forename: Benno
authors.initials: B
authors.lastname: Röthlisberger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D056905:Chromosome Breakpoints; D055028:Comparative Genomic Hybridization; D005260:Female; D015321:Gene Rearrangement; D018095:Germ-Line Mutation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D055815:Young Adult; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000175:diagnosis / Q000235:genetics*; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics*
chemical_list: D055542:alpha-Globins; D055544:beta-Globins