1/6. Hb Suan-Dok [alpha109(G16)Leu-->Arg; CTG-->CGG (alpha2)] described in a patient of African ancestry.A 58-year-old Black female from Curacao (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.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
2/6. Hb Oegstgeest [alpha104(G11)Cys-->Ser (alpha1)]. A new hemoglobin variant associated with a mild alpha-thalassemia phenotype.A microcytic hypochromic anemic state was observed in an 8-year old Black female of Surinam origin during pre-operative Hb S [beta6(A3)Glu-->Val] screening. Her high zinc protoporphyrin (ZPP) level suggested a chronic iron depletion but, in contrast, the high red blood cell (RBC) count (5.85 x 10(12)/L) was indicative of a possible coexisting thalassemia. No abnormal hemoglobin (Hb) bands were present on high performance liquid chromatography (HPLC) or alkaline electrophoresis and the Hb A2 level was normal. Break point polymerase chain reaction (PCR) failed to reveal any of the common alpha-thalassemia (thal) mutations but selective dna sequencing of both alpha-globin genes disclosed a TGC-->AGC transversion at codon 104 of the alpha1 gene. cystine at codon 104 is involved in alpha/beta globin contact and has been described to be a critical amino acid of the alpha2 chain when substituted by a tyrosine (Hb Sallanches), inducing Hb H (beta4) disease in the homozygous state. Our heterozygous patient had a moderate anemia of 12.2 g/dL and a borderline haptoglobin suggesting some degree of hemolysis.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
3/6. The first case of Hb E-Saskatoon associated with Hb Lepore-baltimore found in spain.Hb E-Saskatoon [beta22(B4)Glu-->Lys] does not cause any clinical symptoms in the heterozygous state. The homozygous state shows moderate phenotype expression. It has also been detected in association with beta-thalassemia. We present the first case of Hb E-Saskatoon associated with Hb Lepore-baltimore. This unusual combination of mutations does not aggravate the clinical picture, as only microcytosis and hypochromia have been observed. Hb E-Saskatoon can only be correctly characterized by ion exchange high performance liquid chromatography (HPLC) or by dna sequencing.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
4/6. Hb Amsterdam [alpha32(B13)Met--Ile (alpha2)]: a new unstable variant associated with an alpha-thalassemia phenotype and a new African polymorphism.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.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
5/6. alpha-thalassemia phenotype induced by the new IVS-II-2 (T --> A) splice donor site mutation on the alpha2-globin gene.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.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
6/6. Hemoglobin Loves Park [beta68 (E12) Leu-->Phe]: report of five cases including one originating from a de novo mutation.Hemoglobin (Hb) Loves Park [beta68 (E12) Leu-->Phe] was identified in a 2-year-old Portuguese boy with anemia, microcytosis, and hypochromia. This Hb variant was detected by isoelectric focusing and quantified by reverse-phase high-performance liquid chromatography (HPLC) (48.4%), and the dna mutation was identified by HBB (beta-globin gene) sequencing. Hematological and biochemical analyses performed on his parents revealed normal hematological parameters and normal hemoglobin and globin chain profiles. dna sequence analysis of the HBB gene of both parents showed the absence of the Hb Loves Park mutation. Study of the haplotypes in the beta-globin gene cluster confirmed parenthood. Moreover, paternity was confirmed by the study of nine short tandem repeats (STRs) and four variable-number tandem repeat (VNTRs) loci. The most likely explanation for these results is that the Hb Loves Park mutation has occurred de novo in this family. The original American cases of Hb Loves Park, from a family of Italian origin, which were never published, as well as two additional cases, are also included in this report. Functional studies revealed that Hb Loves Park is stable and has a decreased oxygen affinity.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |