| Autor: |
Assaf N; Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon.; Faculty of Medicine, American University of Beirut, Beirut, Lebanon., El Zibaoui R; Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon., Monsef C; Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon.; Faculty of Medicine, American University of Beirut, Beirut, Lebanon., Abi Nassif T; Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon., Abboud M; Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon., Yazbek S; Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon. |
| Abstrakt: |
Alpha and Beta Thalassemia are autosomal recessive anemias that cause significant morbidity and mortality worldwide, especially in the Middle East and North Africa (MENA) region where carrier rates reach up to 50%. We report the case of two siblings of Palestinian origin born who presented to our tertiary healthcare center for the management of severe transfusion dependent hemolytic anemia. Before presentation to our center, the siblings were screened for a-thalassemia using the Alpha-globin StripAssay. They were found to carry the α2 polyA-1 [AATAAA > AATAAG] mutation in the heterozygous form, which was insufficient to make a diagnosis. No pathogenic variants were detected on Sanger sequencing of the HBB gene. Full sequencing of the a-gene revealed compound heterozygous variants ( HBA1 :c.119_121delCCA and the previously detected HBA2 :c.*+94A > G Poly A [A->G]) with trans inheritance. This report highlights the impact of non-deletional mutations on α-globin chain stability. The compound heterozygosity of a rare α-globin chain pathogenic variant with a polyadenylation mutation in the probands leads to clinically severe a-thalassemia. Due to the high carrier status, the identification of rare mutations through routine screening techniques in our populations may be insufficient. Ongoing collaboration among hematologists, medical geneticists, and counselors is crucial for phenotypic-genotypic correlation and assessment of adequate genetic testing schemes. |
