RESUMO
We have reported the first Tunisian case of triosephosphate isomerase (TPI) deficiency in a 2-year-old girl. She was the first child of a nonconsanguineous couple. The disease included a neonatal onset of chronic hemolytic anemia, recurrent low-respiratory infections then progressive neurological involvement. The diagnosis was made after her death from the TPI values of her parents who exhibited intermediate enzyme deficiency. Molecular study of TPI genes showed that the father and the mother are heterozygous for Glu105Asp mutation. Pediatricians must be alert to the differential diagnosis in patients having hemolytic anemia and other concomitant manifestations.
Assuntos
Anemia Hemolítica Congênita não Esferocítica/complicações , Anemia Hemolítica Congênita não Esferocítica/diagnóstico , Erros Inatos do Metabolismo dos Carboidratos/complicações , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Doenças Neuromusculares/etiologia , Triose-Fosfato Isomerase/deficiência , Substituição de Aminoácidos , Anemia Hemolítica Congênita não Esferocítica/genética , Erros Inatos do Metabolismo dos Carboidratos/genética , Pré-Escolar , Diagnóstico Diferencial , Evolução Fatal , Feminino , Genes Recessivos , Humanos , Lactente , Recém-Nascido , Masculino , Mutação de Sentido Incorreto , Pais , Triose-Fosfato Isomerase/genética , TunísiaRESUMO
BCL11A was the focus of recent studies on its inhibiting effect when bound onto the ß-globin cluster in the mechanism of hemoglobin switching and HbF downregulation. We examined a cohort of 10 patients displaying different HbF levels and short deletions within the γß-δ intergenic region to find a possible correlation with the BCL11A binding site located 5' to the δ-globin gene. Precise characterization of deletions was achieved using a custom DNA-array chip and breakpoint sequencing. The α-globin cluster and major SNP associated with HbF expression were genotyped. Our results show that the loss of the BCL11A binding domain located 5' to the δ-globin gene is correlated with a strong HbF difference (mean+2.7 g/dL, ratio 2.81). This result provides evidence for the use of BCL11A level down-regulation or this domain blockage for new therapies in sickle cell disease and ß-thalassemia major patients.
Assuntos
Proteínas de Transporte/metabolismo , Hemoglobina Fetal/genética , Proteínas Nucleares/metabolismo , Globinas delta/genética , Globinas delta/metabolismo , Adolescente , Adulto , Sítios de Ligação , Criança , Pré-Escolar , Feminino , Hemoglobina Fetal/metabolismo , Deleção de Genes , Expressão Gênica , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Ligação Proteica , Proteínas Repressoras , Adulto JovemRESUMO
The preparation of a prenatal diagnosis in a family of North-African origin in which a child received a bone marrow transplant for ß-thalassemia major (ß-TM), prompted us to make the molecular diagnosis in the parents and siblings. Molecular and phenotype assays were carried on blood samples from the parents and the proband's sister. The father, a 45-year-old man, was found to be heterozygous for a rare mutation in exon 2 [codon 46 (+A), HBB:c.138_139insA] creating a frameshift, while the mother and sister were found to be carriers of the common codon 39 (C>T) stop mutation (HBB:c.118C>T). Because of the bone marrow transplant, proband genotyping was done from a buccal swab and revealed that he is a compound heterozygote for both the codon 46 and codon 39 mutations. In the parents and sister, hematological parameters were those of a thalassemia minor in agreement with the two ß(0) mutations found in the family.