RESUMEN
Hb Groene Hart [alpha119(H2)Pro-->Ser, CCT-->TCT (alpha1)] has been reported in heterozygotes of Moroccan origin and also in association with the common -alpha(3.7) deletion. In all cases, the mutated protein was not detectable but was apparently associated with a mild alpha-thalassemia (thal) phenotype, presumably due to a modification of the alpha-globin chain domain that is recognized by the a hemoglobin stabilizing protein (AHSP). The present case of Hb Groene Hart homozygosity, confirms that the alpha-thal phenotype is associated with this alpha-globin chain. Hb Groene Hart must be quite frequent not only in Morocco but probably also among the northern African coastal population.
Asunto(s)
Variación Genética , Hemoglobinas Anormales/genética , Polimorfismo de Nucleótido Simple , Talasemia/genética , Sustitución de Aminoácidos , Homocigoto , Humanos , Países Bajos , Fenotipo , Prolina , Serina , Talasemia/sangreRESUMEN
We present a family of North European extraction referred for a refractory non iron depleted microcytic anemia. The proband, a 36 year-old male, presented with chronic borderline anemia and microcytic hypochromic parameters. No abnormal hemoglobin (Hb) fractions were observed on high performance liquid chromatography (HPLC) or on alkaline electrophoresis. Gap-polymerase chain reaction (gap-PCR) excluded the seven common alpha-thalassemia (thal) deletion defects. However, the beta/alpha-globin chain synthesis ratio measured in vitro was unbalanced, indicating a reduced expression of the alpha-globin genes. Direct sequencing of the alpha-globin genes revealed heterozygosity for a T --> A transversion at the IVS-II-2 position of the alpha2 gene. This is the first IVS-II splice donor site mutation described on the alpha2-globin gene.
Asunto(s)
Empalme Alternativo , Anemia Hipocrómica/genética , Eliminación de Gen , Globinas/genética , Hemoglobinas/genética , Mutación Puntual , Talasemia alfa/genética , Adulto , Alelos , Anemia Hipocrómica/sangre , Enfermedad Crónica , Análisis Mutacional de ADN , Salud de la Familia , Humanos , Masculino , Linaje , Fenotipo , Subunidades de Proteína/genética , Talasemia alfa/sangreRESUMEN
We have characterized a new abnormal hemoglobin (Hb) at position 32 of the alpha-globin chain. The proband, a 38-year-old woman of Surinamese Black ancestry, was referred to the Academic Hospital in Amsterdam, The Netherlands, after 3 years of Prednisone treatment in Surinam. Kidney failure was diagnosed at the Nephrology Department, Free University Medical Center, Amsterdam, The Netherlands; the cortisone treatment was interrupted and dialysis was started. At this stage, a microcytic hypochromic anemia was observed with high reticulocyte (40%) and ferritin (500 microg/L) levels, and hemoglobinopathy was suspected. No abnormal bands were visible on alkaline electrophoresis and high performance liquid chromatography (HPLC). The Hb A2 level was normal (2.7%) and the erythrocyte count was low (3.59 x 10(12)/L) with a normal haptoglobin level (68 mg/100 mL). None of the common alpha-thalassemia (thal) deletion defects were present. The beta-globin gene sequence was normal but the alpha2-globin gene sequence revealed an ATG-->ATA transition at codon 32, changing the methionine into an isoleucine residue. The mutation, called Hb Amsterdam, was observed in the mother of the proband, who was also heterozygous for the--alpha3.7-thal deletion and affected by a moderate microcytic hypochromic anemia. Both Hb Amsterdam and the--alpha(-3.7) allele were found in association with a new polymorphism, IVS-I-39 (C-->T), previously observed in our laboratory in seven patients of African origin, on both the alpha1 and alpha2 genes. In addition, Hb Amsterdam was also associated with the common African alpha2 polymorphism (G-->CTCGGCCC at position 7238 and T-->G at position 7174). Hb Amsterdam is the first mutation ever described at codon alpha32, a position involved in alpha1/beta1 interaction. The possibility of a contribution of this mutation to the nephropatic state of the proband is discussed.
Asunto(s)
Hemoglobinas Anormales/genética , Polimorfismo Genético , Talasemia alfa/genética , Adulto , África , Anemia Hipocrómica/genética , Población Negra/genética , Salud de la Familia , Femenino , Variación Genética , Humanos , Fenotipo , Mutación Puntual , Insuficiencia Renal/diagnóstico , Insuficiencia Renal/terapia , Eliminación de Secuencia , Talasemia alfa/etnologíaRESUMEN
An abnormal hemoglobin (Hb) fraction was observed during a high performance liquid chromatographic (HPLC) Hb A1c control for diabetes mellitus in a 56-year-old north European woman. Family analyses revealed the abnormal fraction in three of her five siblings and in her son. Elevated Hb and packed cell volume (PCV) values and red blood cell (RBC) counts were present in all carriers. No histories of anemia, hemolytic or circulatory episodes were reported. The abnormal Hb fraction estimated at 40%, migrated just below Hb F on alkaline electrophoresis and overlapped the Hb A2 peak on cation exchange HPLC. Direct sequencing of the beta-globin genes revealed a new GAC --> TAC transversion in heterozygous form at codon 94 of the beta-globin gene. Based on the hematological/biochemical data and the decreased P50 value, we conclude that the new variant is a stable Hb associated with a slightly elevated oxygen affinity.
Asunto(s)
Diabetes Mellitus/genética , Variación Genética/genética , Hemoglobinas Anormales/genética , Mutación Puntual/genética , Sustitución de Aminoácidos/genética , Cromatografía Líquida de Alta Presión , Análisis Mutacional de ADN , Diabetes Mellitus/sangre , Salud de la Familia , Femenino , Hemoglobina A/análisis , Heterocigoto , Humanos , Persona de Mediana Edad , Países Bajos/epidemiología , LinajeRESUMEN
A 58-year-old Black female from Curaçao (West Indies) was recently referred to our Laboratory for a persistent microcytic hypochromic anemia. An analysis 13 years earlier had shown no abnormal hemoglobin (Hb) fractions and a balanced beta/alpha synthetic ratio. The hematological indices were again compatible with thalassemia and no abnormal fractions were observed on electrophoresis or high-performance liquid chromatography (HPLC). None of the seven common alpha-thalassemia (thal) deletion defects were present. Direct sequencing of the alpha2 gene revealed a CTG-->CGG single base substitution at codon 109. This mutation was previously described in a Thai patient (Hb Suan-Dok), inducing Hb H disease in association with a - -(SEA) allele. In contrast with earlier reports we were unable to identify any native Hb fraction. The balanced beta/alpha ratio indicated that alpha2-Suan-Dok is formed but does not form tetramer formation unless alpha-thal is present.
Asunto(s)
Anemia Hipocrómica/genética , Hemoglobinas Anormales/genética , Mutación Puntual/genética , Población Negra , Femenino , Humanos , Persona de Mediana Edad , Estructura Cuaternaria de Proteína/genética , Talasemia alfa/genéticaRESUMEN
The hemoglobin (Hb) pattern of a 32-year-old Somali male living in The Netherlands, during routine diabetes mellitus monitoring, showed two more peaks in addition to the characteristic heterozygous Hb A/S pattern. A major peak of 15% faster than Hb A, and a minor one of 10.8%, overlapping Hb A2 and the glycated Hb S1c fraction were present. The patient was not anemic or microcytic but had a low haptoglobin level, possibly indicating a slightly elevated red blood cell (RBC) turnover. Hb S was confirmed by a sickle test and at the DNA level. The DNA sequence of the alpha1 gene revealed a C-->G transversion at position 89, changing the local positively charged histidine to a neutral glutamine. This mutant has been previously described in a Yemenite woman and two apparently unrelated Somali males. Our case is the first showing Hb Buffalo in combination with Hb S and a G6PD deficiency, and is again observed in a Somali. No functional abnormalities associated with mutations at this amino acid residue are reported in the literature. Also, in this case no sign of any hematological abnormalities that could not be explained by the Hb S heterozygosity G6PD deficiency was found. The abnormal alpha chain is expressed at the expected rate and without thalassemic effect or instability. The mutated alpha chain seems to associate with a slight preference to the beta(A) (15%) rather than with the beta(S) counterpart. The sum of both Hb A(Buffalo) and Hb S(Buffalo) results in about 19-20% of total Hb. This figure is in agreement with a stable mutant of the alpha1 gene.