Assuntos
Elementos Facilitadores Genéticos , Hemoglobina H/genética , alfa-Globinas/genética , Talassemia alfa/genética , Adulto , Alelos , Cromatina/genética , Cromatina/ultraestrutura , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 16/ultraestrutura , Eritroblastos/patologia , Eritropoese , Feminino , Deleção de Genes , Regulação da Expressão Gênica , Genótipo , Hemoglobina E/genética , Hemoglobina H/análise , Humanos , Masculino , Linhagem , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Deleção de Sequência , Suriname/etnologia , alfa-Globinas/biossíntese , Talassemia alfa/sangue , Globinas beta/genéticaRESUMO
We report two families, members of which are carriers of a novel hemoglobin (Hb) variant that was named Hb Olivet [α13(A11)AlaâThr (α1) (GCC > ACC); HBA1: c.40G > A; p.Ala14Thr]. The analysis of these cases allowed a clear description of this anomaly that behaves as a silent Hb. In the first family, of Portuguese ethnicity living in France, the proband, a 24-year-old male and his 57-year-old mother, both appeared to be carriers. The son presented with borderline mean corpuscular volume (MCV), while the mother was normocytic and normochromic. Hemoglobin separation on capillary electrophoresis (CE) was normal, while a slightly asymmetric peak was observed on high performance liquid chromatography (HPLC). In a second family, originally from Surinam but living in The Netherlands, the proband, a 6-year-old girl, showed a mild microcytosis at low ferritin levels. The abnormal Hb was inherited from the mother who was clearly iron depleted, was not present in the sister and brother of the proband. The microcytic hypochromic anemia was only shown in two out of a total of four carriers. It therefore seems likely that iron depletion is causative as two carriers are completely normal. Characterization and genotype/phenotype correlation are briefly described.
Assuntos
Estudos de Associação Genética , Hemoglobinopatias/patologia , Hemoglobinas Anormais/genética , Mutação/genética , Criança , Família , Feminino , França/epidemiologia , Hemoglobinopatias/sangue , Hemoglobinopatias/genética , Heterozigoto , Humanos , Deficiências de Ferro , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Portugal/etnologia , Suriname/etnologia , Adulto JovemRESUMO
OBJECTIVES: We conducted population specific confidential enquiries among immigrants who had never experienced hemoglobinopathies, to study the reliability of this approach in estimating the wish for primary prevention by prenatal diagnosis and selective abortion. METHODS: We collected data from Surinamese Hindustanis (n = 119), Surinamese and Antillean Afro-Americans (n = 105) and North Africans (mainly Moroccans) (n = 102), living in Holland. We also interviewed 105 informed individuals of different ethnicities, all members of the multi-ethnic patients and carriers' organization 'OSCAR Nederland'. RESULTS: On average, 68% of the Surinamese Hindustanis and 42% of the Surinamese Afro-Americans were in favor of selective abortion in case of affected pregnancy. Remarkably, 77% of the last group wanted to be tested for carrier diagnostics and 67% declared to have knowledge of the disease before they were informed. Only 16% of the Moroccans were in favor of selective abortion in case of an affected fetus, while 79% wanted to have blood analysis to establish their carrier status. CONCLUSIONS: The apparently limited wish for selective abortion expressed by Moroccans is in contrast with the high number of illegal abortions reported among married women in Morocco (39%). The wish for selective abortion among informed members of the patients' organization was more than 80%.
Assuntos
Atitude , Emigração e Imigração , Hemoglobinopatias/prevenção & controle , Aborto Terapêutico/psicologia , Anemia Falciforme/prevenção & controle , Árabes/etnologia , Feminino , Triagem de Portadores Genéticos , Humanos , Marrocos/etnologia , Países Baixos , Fenobarbital/análogos & derivados , Gravidez , Diagnóstico Pré-Natal/psicologia , Suriname/etnologia , Talassemia/prevenção & controle , Índias Ocidentais/etnologiaRESUMO
We describe the characterization of a novel 7.9 kb deletion that eliminated one of the duplicated alpha-globin genes, causing an alpha+-thalassaemia phenotype in two independent carriers of Suriname-Indian origin. The molecular characterization of the deletion breakpoint fragment revealed neither involvement of Alu repeat sequences nor the presence of homologous regions prone to recombination, suggesting a non-homologous recombination event. This alpha+-thalassaemia deletion was found to give rise to an atypical haemoglobin H (HbH) disease characterized by a non-transfusion-dependent moderate microcytic hypochromic anaemia in combination with a poly adenylation signal mutation of the alpha-globin gene (alpha2 AATAAA --> AATA-- --).