title: Combination of a triple alpha-globin gene with beta-thalassemia in a gypsy family: importance of the genetic testing in the diagnosis and search for a donor for bone marrow transplantation for one of their children.
abstract: BACKGROUND
  The simultaneous presence of a heterozygous β-thalassemia with α-gene triplication may cause anything from a thalassemia trait to thalassemia intermedia of mild to moderate severity.
  
  
  METHODS
  An 8-month-old ethnic Gypsy male infant with failure to thrive from birth, mild jaundice and splenomegaly. Clinical signs were compatible with severe microcytic anemia requiring bi-monthly blood transfusions. The β-thalassemia gene analysis found homozygous mutation IVS-I-110 (G>A) (c.93-21G>A) in intron 1 of the hemoglobin beta globin gene and a non-pathogenic sequence variant (single nucleotide polimorfism (SNP) Rs1609812). In addition, the patient had α gene triplication (ααα(anti 3.7)/αα) caused by double heterozygosity for a 3.7 kb fragment that contained only the hemoglobin alpha globin gene-2 gene. This finding led to screening and follow up in first-degree relatives, twin brothers and a sister and parents to provide them with appropriate genetic counseling. Nowadays, new horizons could open a new therapeutic management until definitive cure of these diseases through gene therapy or mutation-specific genome editing.
  
  
  CONCLUSIONS
  Genetic testing can provide an early diagnosis and facilitates the search for a suitable donor for transplantation.
authors.affiliation: Department of Hematology, Hospital Universitario Miguel Servet, C/Padre Arrupe, s/n, planta 4ª, 50009, Saragossa, Spain. floryuscebrian@gmail.com.
authors.forename: Flor
authors.initials: F
authors.lastname: Yus Cebrian
authors.affiliation: Department of Hematology, Hospital Universitario Miguel Servet, C/Padre Arrupe, s/n, planta 4ª, 50009, Saragossa, Spain.
authors.forename: María del Valle
authors.initials: Mdel V
authors.lastname: Recasens Flores
authors.affiliation: Genetics Unit, Department of Clinical Biochemistry, Hospital Universitario Miguel Servet, Saragossa, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Izquierdo Álvarez
authors.affiliation: Department of Hematology, Hospital Universitario Miguel Servet, C/Padre Arrupe, s/n, planta 4ª, 50009, Saragossa, Spain.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Parra Salinas
authors.affiliation: Department of Pediatrics, Hospital Universitario Miguel Servet, Saragossa, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodriguez-Vigil Iturrate
mesh_terms: D001782:Blood Donors; D016026:Bone Marrow Transplantation / Q000379:methods; D005192:Family Health; D005260:Female; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D005810:Multigene Family; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011174:Portugal; D006178:Romani People / Q000235:genetics*; D055542:alpha-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy
chemical_list: D055542:alpha-Globins
keywords: Alpha-globin gene triplication; Beta thalassemia major; Iron overload; Microcytic anemia; Splenomegaly; Thalassemia minor