RESUMO
We report a new ß-globin chain variant: Hb Meylan [ß73(E17)Asp â Phe; HBB: c.220G>T; c.221A>T]. The new variant results from a double nucleotide mutation at the same codon. The possible molecular mechanisms are discussed.
Assuntos
Hemoglobinas Anormais/genética , Mutação Puntual , Globinas beta/genética , Sequência de Bases , Códon , Feminino , Conversão Gênica , Humanos , Pessoa de Meia-Idade , Dados de Sequência MolecularRESUMO
We report two new variants of the δ-globin gene: Hb A(2)-Saint-Etienne [δ14(A11)LeuâPro] and Hb A(2)-Marseille [δ22(B4)AlaâLys]. The first variant has a low rate of expression, the second results from a double nucleotide mutation on the same codon.
Assuntos
Hemoglobina A2/genética , Mutação , Globinas delta/genética , Sequência de Aminoácidos , Sequência de Bases , DNA/genética , Feminino , Hemoglobina A2/química , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Análise de Sequência de DNA , Talassemia beta/genética , Globinas delta/químicaRESUMO
We report two new hemoglobin (Hb) variants; one causing an impairment of the N-terminal glycation of the ß-globin chain and the other a hematological phenotype of α-thalassemia (α-thal). The first variant is Hb Aix-les-Bains [ß5(A2)ProâLeu] and the second Hb Dubai [α122(H5)HisâLeu (α2)]. These two new Hb variants were detected by chromatographic and electrophoretic methods and characterized by molecular studies. Hb Dubai gives an α-thalassemic phenotype and should be routinely detected for preventing severe Hb H disease in couples at-risk for α-thal.
Assuntos
Substituição de Aminoácidos/genética , Hemoglobina A2/genética , Mutação Puntual/genética , alfa-Globinas/genética , Talassemia alfa/genética , Globinas beta/genética , Idoso de 80 Anos ou mais , Sequência de Bases , Códon , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Talassemia alfa/diagnósticoRESUMO
We present here five new hemoglobin (Hb) variants which have been identified during routine Hb analysis before their genotypic characterization. Four of these result from a classical missense mutation: Hb Canuts [alpha85(F6)Asp-->His (alpha1)], Hb Ambroise Pare [alpha117(GH5)Phe-->Ile (alpha2)], Hb Beaujolais [beta84(EF8)Thr-->Asn] and HbA(2)-North Africa [delta59(E3)Lys-->Met]. The last one, Hb Monplaisir [beta147 (Tyr-Lys-Leu-Ala-Phe-Phe-Leu-Leu-Ser-Asn-Phe-Tyr-158-COOH)], results from a frameshift mutation at the stop codon of the beta-globin gene which leads to a modified C-terminal sequence in the beta-globin chain. None of these variants seem to have a particular clinical expression in the heterozygous state. The circumstances of the discovery of these five new Hb variants emphasize the fact that an association of techniques is necessary for a complete screening of Hb variants during routine Hb analysis. Globin chain separation by reversed phase liquid chromatography (RP-LC) appears to be the most relevant method.
Assuntos
Mutação da Fase de Leitura , Hemoglobinas Anormais/genética , Mutação de Sentido Incorreto , Sequência de Aminoácidos , Substituição de Aminoácidos , Cromatografia Líquida de Alta Pressão/métodos , Análise Mutacional de DNA , Índices de Eritrócitos , Variação Genética , Genótipo , Hemoglobinopatias/sangue , Hemoglobinopatias/genética , HumanosRESUMO
Despite the fact that mutations in the human beta-globin gene cluster are essentially point mutations, a significant number of large deletions have also been described. We present here four new large deletions in the beta-globin gene cluster that have been identified on patients displaying an atypical hemoglobin phenotype (high HbF) at routine analysis. The first deletion, which spreads over 2.0 kb, removes the entire beta-globin gene, including its promoter, and is associated with a typical beta-thal minor phenotype. The three other deletions are larger (19.7 to 23.9 kb) and remove both the delta and beta-globin genes. Phenotypically, they look like an HPFH-deletion as they are associated with normal hematological parameters. The precise localization of their 5' and 3' breakpoints gives new insights about the differences between HPFH and (deltabeta)(0)-thalassemia at the molecular level. The importance of detection of these deletions in prenatal diagnosis and newborn screening of hemoglobinopathies is also discussed.
Assuntos
Deleção de Genes , Talassemia/genética , Globinas beta/genética , Adulto , Sequência de Bases , Feminino , Hemoglobina Fetal/análise , Hemoglobina Fetal/genética , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Família Multigênica , Fenótipo , Talassemia/diagnóstico , Adulto Jovem , Globinas beta/análiseRESUMO
We report here two new beta(0)-thalassemic mutations. In the first case, a deletion of two nucleotides (-CC) at codon 142 was found in a French Caucasian woman. In the second case, an insertion of a single nucleotide (+T) at codon 45 was found in a Turkish girl. In both cases, no dominant thalassemia-like phenotype was observed.
Assuntos
Códon/genética , Globinas/genética , Mutação , Talassemia beta/genética , Idoso , Sequência de Aminoácidos , Criança , Primers do DNA , Feminino , Mutação da Fase de Leitura , Humanos , Dados de Sequência Molecular , Mutagênese Insercional , Reação em Cadeia da Polimerase , Deleção de SequênciaRESUMO
A new hemoglobin (Hb) variant in the heterozygous state, Hb Al-Hammadi Riyadh [codon 75 (GAC-->GTC); alpha75(EF4)Asp-->Val (alpha2)] corresponding to an A-->T transversion on the second exon of the alpha2-globin gene, is described. The variant was characterized by DNA sequencing and mass spectrometry (MS). The variant was found during a routine Hb analysis for anemia in a 16-month-old boy who lived in Riyadh, Kingdom of Saudi Arabia.
Assuntos
Anemia/genética , Globinas/genética , Hemoglobinas Anormais/genética , Mutação de Sentido Incorreto , Mutação Puntual , Substituição de Aminoácidos , Anemia/sangue , Cromatografia Líquida de Alta Pressão , Códon/genética , Globinas/química , Hemoglobinas Anormais/química , Humanos , Lactente , Focalização Isoelétrica , Masculino , Reação em Cadeia da Polimerase , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
A new G(gamma) hemoglobin (Hb) variant, Hb F-Bron [gamma20(B2)Val-->Ala] on the first exon of the G(gamma)-globin gene is described. The variant was characterized by DNA sequencing and mass spectrometry (MS). Hematological abnormalities included hypochromia and microcytosis and were probably caused by an interaction with an alpha-thalassemia (thal) (3.7 kb) deletion in the heterozygous state.
Assuntos
Hemoglobina Fetal/genética , Hemoglobinas Anormais/genética , Mutação de Sentido Incorreto , Anemia Hipocrômica/genética , Análise Mutacional de DNA , Variação Genética , Globinas/genética , Humanos , Recém-Nascido , Masculino , Talassemia alfa/genéticaRESUMO
A new mutation of the beta-globin gene initiation codon, ATG-->AAG (Met-->Tyr), is reported in a man originating from the southeast of France. Typical hematological findings of beta-thalassemia (thal) trait were found. We emphasize the importance of characterizing uncommon beta-thal mutations for genetic counseling.
Assuntos
Códon de Iniciação/genética , Globinas/genética , Mutação Puntual , Talassemia beta/genética , Adulto , França , Humanos , Masculino , População BrancaRESUMO
Two new hemoglobin (Hb) variants: Hb Brem-sur-Mer [codon 9 (TCT-->TAT); beta9(A6)Ser-->Tyr] on the first exon of the beta-globin gene and Hb Passy [codon 81 (TCC-->CCC); alpha81(F2)Ser-->Pro (alpha2)] on the second exon of the alpha2-globin gene, are described. The two variants were characterized by DNA sequencing and mass spectrometry (MS). Hematological abnormalities: microcytosis and hypochromia were found only in the carrier of Hb Passy. In the absence of an association with an alpha-thalassemic deletion or mutation, the mutation 81(F2)Pro could induce a possible alpha-thalassemia (thal).
Assuntos
Substituição de Aminoácidos/genética , Códon/genética , Éxons/genética , Hemoglobinas Anormais/genética , Mutação Puntual/genética , Aminoácidos/genética , Anemia Hipocrômica/genética , Feminino , Humanos , Masculino , Talassemia alfa/genéticaRESUMO
Two new beta-globin chain variants: Hb Tripoli: codon 26, GAG-->GCG [beta26(B8)Glu-->Ala] and Hb Tizi-Ouzou: codon 29, GGC-->AGC [beta29(B11)Gly-->Ser] are described on the first exon of the beta-globin gene. The two variants are characterized by DNA sequencing and mass spectrometry (MS). Hematological abnormalities were found in the two carriers. The presence of microcytosis and hypochromia is explained by an additional homozygous 3.7 kb alpha(+) thalassemic deletion for the carrier of Hb Tizi-Ouzou. Hb Tizi-Ouzou showed a slight instability in vitro. The same hematological abnormalities associated with anemia are difficult to explain for Hb Tripoli's carrier in the absence of an alpha-globin genes abnormality and could suggest a possible abnormal splicing.
