RESUMEN
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.
Asunto(s)
Mutación del Sistema de Lectura , Hemoglobinas Anormales/genética , Mutación Missense , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Cromatografía Líquida de Alta Presión/métodos , Análisis Mutacional de ADN , Índices de Eritrocitos , Variación Genética , Genotipo , Hemoglobinopatías/sangre , Hemoglobinopatías/genética , HumanosRESUMEN
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.
Asunto(s)
Codón/genética , Globinas/genética , Mutación , Talasemia beta/genética , Anciano , Secuencia de Aminoácidos , Niño , Cartilla de ADN , Femenino , Mutación del Sistema de Lectura , Humanos , Datos de Secuencia Molecular , Mutagénesis Insercional , Reacción en Cadena de la Polimerasa , Eliminación de SecuenciaRESUMEN
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.
Asunto(s)
Anemia/genética , Globinas/genética , Hemoglobinas Anormales/genética , Mutación Missense , Mutación Puntual , Sustitución de Aminoácidos , Anemia/sangre , Cromatografía Líquida de Alta Presión , Codón/genética , Globinas/química , Hemoglobinas Anormales/química , Humanos , Lactante , Focalización Isoeléctrica , Masculino , Reacción en Cadena de la Polimerasa , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
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.
Asunto(s)
Codón Iniciador/genética , Globinas/genética , Mutación Puntual , Talasemia beta/genética , Adulto , Francia , Humanos , Masculino , Población BlancaRESUMEN
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.
Asunto(s)
Hemoglobina Fetal/genética , Hemoglobinas Anormales/genética , Mutación Missense , Anemia Hipocrómica/genética , Análisis Mutacional de ADN , Variación Genética , Globinas/genética , Humanos , Recién Nacido , Masculino , Talasemia alfa/genéticaRESUMEN
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).
Asunto(s)
Sustitución de Aminoácidos/genética , Codón/genética , Exones/genética , Hemoglobinas Anormales/genética , Mutación Puntual/genética , Aminoácidos/genética , Anemia Hipocrómica/genética , Femenino , Humanos , Masculino , Talasemia alfa/genéticaRESUMEN
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.