A NOVEL DELETION/INSERTION CAUSED BY A REPLICATION ERROR IN THE beta-GLOBIN GENE LOCUS CONTROL REGION

作者：Joly Philippe; Lacan Philippe; Garcia Caroline; Meley Roland; Pondarre Corinne; Francina Alain^*

来源：Hemoglobin, 2011, 35(4): 316-322.

DOI：10.3109/03630269.2011.571331

• (epsilon gamma delta beta)(0)-Thalassemia [(epsilon gamma delta beta)(0)-Thal]
• beta-Locus control region (beta-LCR)
• Deletion
• Insertion
• Multiplex-ligation probe amplification (MLPA)

Deletions in the beta-globin locus control region (beta-LCR) lead to (epsilon gamma delta beta)(0)-thalassemia [(epsilon gamma delta beta)(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 beta-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 beta-LCR deletion found in a French Caucasian patient which removes DNase I hypersensitive site 2 (HS2) to HS4 of the beta-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 alpha-thal trait. Consequently, a complete alpha- and beta-globin gene cluster analysis is required to prevent a potentially damaging misdiagnosis in genetic counselling.

• 出版日期2011