title: A novel deletion/insertion caused by a replication error in the β-globin gene locus control region.
abstract: Deletions in the β-globin locus control region (β-LCR) lead to (εγδβ)(0)-thalassemia [(εγδβ)(0)-thal]. In patients suffering from these rare deletions, a normal hemoglobin (Hb), phenotype is found, contrasting with a hematological thalassemic phenotype. Multiplex-ligation probe amplification (MLPA) is an efficient tool to detect β-LCR deletions combined with long-range polymerase chain reaction (PCR) and DNA sequencing to pinpoint deletion breakpoints. We present here a novel 11,155 bp β-LCR deletion found in a French Caucasian patient which removes DNase I hypersensitive site 2 (HS2) to HS4 of the β-LCR. Interestingly, a 197 bp insertion of two inverted sequences issued from the HS2-HS3 inter-region is present and suggests a complex rearrangement during replication. Carriers of this type of thalassemia can be misdiagnosed as an α-thal trait. Consequently, a complete α- and β-globin gene cluster analysis is required to prevent a potentially damaging misdiagnosis in genetic counselling.
authors.affiliation: Unité de Pathologie Moléculaire du Globule Rouge, Hôpital Edouard Herriot, Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Joly
authors.forename: Philippe
authors.initials: P
authors.lastname: Lacan
authors.forename: Caroline
authors.initials: C
authors.lastname: Garcia
authors.forename: Roland
authors.initials: R
authors.lastname: Meley
authors.forename: Corinne
authors.initials: C
authors.lastname: Pondarré
authors.forename: Alain
authors.initials: A
authors.lastname: Francina
mesh_terms: D000328:Adult; D001483:Base Sequence; D004261:DNA Replication / Q000235:genetics; D006801:Humans; D019901:Locus Control Region / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D021141:Nucleic Acid Amplification Techniques / Q000379:methods; D017384:Sequence Deletion; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics
chemical_list: D055544:beta-Globins