title: Characterization of two unique α-globin gene cluster deletions causing α-thalassemia in Israeli Arabs.
abstract: The molecular basis of α-thalassemia (α-thal) is complex. The use of multiplex ligation-dependent probe amplification (MLPA) has offered the possibility of identifying more gene deletions causing α-thal. Our objective was to determine the molecular basis of two patients with Hb H (β4) disease. By using MLPA in combination with comparative genomic hybridization (CGH) we identified two novel α-globin gene cluster deletions: a 30 kb deletion (patient 1) we refer to as - -(JAL) and a large 216 kb deletion (patient 2) we refer to as - -(LOD). Patient 1 was a compound heterozygote for - -(JAL) and -α(3.7) (rightward deletion). Twelve family members of patient 1 carrying the - -(JAL) deletion were available for evaluation: five with - -(JAL)/-α(3.7), four with - -(JAL)/α(Hph I)α and three with - -(JAL)/αα. Their clinical picture of compound heterozygosity was compatible with moderate Hb H disease. In patient 2 (- -(LOD)/-α(3.7)), no additional symptoms were present despite the heterozygous deletion of seven known genes, three non coding RNAs (ncRNAs), four unknown genes and two pseudo genes. Further analysis of more patients with α-thal deletions will have implications for genetic counseling and appropriate therapy.
authors.affiliation: Department of Pediatrics B, Schneider Children's Medical Center of Israel , Petah Tikva , Israel .
authors.forename: Oded
authors.initials: O
authors.lastname: Gilad
authors.forename: Orly
authors.initials: O
authors.lastname: Dgany
authors.forename: Sharon
authors.initials: S
authors.lastname: Noy-Lotan
authors.forename: Tania
authors.initials: T
authors.lastname: Krasnov
authors.forename: Sarah
authors.initials: S
authors.lastname: Elitzur
authors.forename: Serge
authors.initials: S
authors.lastname: Pissard
authors.forename: Iris
authors.initials: I
authors.lastname: Kventsel
authors.forename: Joanne
authors.initials: J
authors.lastname: Yacobovich
authors.forename: Hannah
authors.initials: H
authors.lastname: Tamary
mesh_terms: D018912:Arabs; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002885:Chromosomes, Human, Pair 16; D055028:Comparative Genomic Hybridization; D003241:Consanguinity; D005192:Family Health; D005260:Female; D056426:Genetic Loci; D006447:Hemoglobin H / Q000032:analysis; D006579:Heterozygote; D006801:Humans; D007557:Israel; D005810:Multigene Family; D060885:Multiplex Polymerase Chain Reaction; D010375:Pedigree; D012720:Severity of Illness Index; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000097:blood / Q000235:genetics* / Q000503:physiopathology
chemical_list: D055542:alpha-Globins; D006447:Hemoglobin H
keywords: deletion; α-Globin gene cluster; α-thalassemia (α-thal)