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C Feo

Publications and source records attributed to C Feo.

At least 19 recordsLinked to original sources
PubMed1990

A haemolytic syndrome associated with the complete absence of red cell membrane protein 4.2 in two Tunisian siblings.

We report on the complete absence of protein 4.2 in two Tunisian siblings. The propositus presented with a haemolytic anaemia that evolved in an intermittent fashion until she was cured by splenectomy. Her red cells had a normal morphology, as well as normal deformability upon osmotic gradient ektacytometry. SDS-polyacrylamide gel electrophoresis failed to reveal any protein 4.2. Using anti-protein 4.2 polyclonal antibodies. Western blots were also unable to detect protein 4.2. Preparation of inside out vesicles resulted in no detectable loss of ankyrin. The propositus's sister presented with a haemolytic anaemia but had not undergone splenectomy; she showed the same biochemical features. The two cases presented of missing protein 4.2 are the first ones to be described outside the Japanese population. Considered as homozygotes for some defect that must alter the protein 4.2 gene itself, they exemplify a unique syndrome pertaining neither to elliptocytosis nor to spherocytosis, at least not closely. The parents, who are first cousins and whom we regarded as heterozygotes, were clinically and morphologically normal; they had a normal content of protein 4.2. Therefore, the 4.2 (-) haemolytic anaemia appears as entirely recessive.

Adult↗
PubMed1990

Severe recessive poikilocytic anaemia with a new spectrin alpha chain variant.

A severe neonatal haemolytic anaemia was observed in a propositus from the West Indies. Frequent blood transfusions were required until complete splenectomy was carried out. Blood smears showed predominant poikilocytosis with spherocytes and microcytes as observed in hereditary pyropoikilocytosis. Erythrocytes were completely fragmented after incubation at 45 degrees C. The two asymptomatic parents had normal haematological profiles. The erythrocyte membrane electrophoretic patterns of the splenectomized propositus and her parents were normal. The propositus had a moderate defect in the spectrin (Sp) dimer self-association. Limited tryptic digestion of the propositus' Sp under standard conditions (0 degrees C, 20 h, enzyme-substrate ratio of 1/100) revealed an increased sensitivity to tryptic digestion. The major features detected by one- and two-dimensional electrophoresis gels of Sp tryptic digests were the absence of high molecular weight peptides from the Sp alpha II (48 kDa and 35 kDa peptides) and Sp alpha III (52 kDa peptide) domains with increased amounts of the lower molecular weight peptides from the Sp alpha II and Sp alpha III (29 kDa peptide and 47 kDa peptide) domains respectively. Kinetic studies of Sp tryptic digestion (10 min to 36 h) confirmed the increased tryptic susceptibility of Sp. Immunodetection with specific anti-alpha-chain domain antibodies showed that the highest molecular weight peptides from the alpha II and alpha III domains are released early in digestion, but disappear quickly, with an increase in their corresponding smaller peptides. The molecular weights of the peptides corresponding to the 48 kDa and 35 kDa peptides from the alpha II domain are slightly modified. Peptides from the alpha I and alpha IV domains showed no significant abnormalities. The Sps of both parents were normal. These results indicate that the patient has a novel Sp alpha chain defect, which is probably located in the region of the alpha II domain which adjoins the alpha III domain.

Anemia, Hemolytic, Congenital↗
PubMed1990

Point mutation in the beta-spectrin gene associated with alpha I/74 hereditary elliptocytosis. Implications for the mechanism of spectrin dimer self-association.

alpha I/74 hereditary elliptocytosis (HE) is a subgroup of HE in which patients exhibit an impaired self-association of spectrin dimers and an abnormal proteolytic cleavage of the alpha I domain of spectrin. We studied a family in which the proband presented with a severe neonatal hemolytic anemia with poikilocytosis. Biochemical analysis of erythrocytes from the proband and his family members allowed us to ascertain a diagnosis of homozygosity for alpha I/74 HE in the proband and heterozygosity in his parents and several of their offspring. Results of polymorphism linkage analysis suggested that the defect in this family was located in beta rather than alpha spectrin. We analyzed the 3' end of the beta-spectrin gene of the proband and detected a mutation that changes a codon for alanine to one for proline. Allele-specific oligomer hybridization on slot blots of DNA from other family members confirmed the presence of the mutation only in members heterozygous for the disorder. This is the first example of a point mutation in the beta-spectrin chain that is associated with defective spectrin dimer self-association and an abnormal proteolytic cleavage of the alpha chain. Based on this finding, we propose a model for the mechanism of interaction between the alpha- and beta-spectrin chains.

Amino Acid Sequence↗
PubMed1989

Hemoglobin Athens-Georgia [alpha 2 beta 2 40(C6)Arg----Lys] in association with beta 0-thalassemia in Tunisia.

We describe an Hb Athens-Georgia (Hb A-Ga)/beta 0-thalassemia compound heterozygosity, found in a Tunisian patient. Oxygen binding studies of red cell suspensions of this patient, containing approximately 95% Hb A-Ga, revealed an almost normal oxygen affinity. Nevertheless, dilute solutions of Hb A-Ga showed an increased overall oxygen affinity and decreased heme-heme interaction. This could be explained by a tetrameric hemoglobin with normal oxygen binding properties but with increased dissociation into monomers or dimers, as a consequence of a structural abnormality within the alpha 1 beta 2 interface. Such an interpretation would explain the increased oxygen affinity reported in previous studies performed on heterozygous Hb A/Hb A-Ga patients.

Hemoglobins, Abnormal↗
PubMed1988

Hemoglobin J Guantanamo [alpha 2 beta 2 128 (H6) Ala----Asp] in association with hemoglobin C and alpha-thalassemia in a family from Benin.

Hemoglobin J (HbJ), Guantanamo, which had been described but once in the literature, was found in a family originating from Benin; this second case was found to be in association with hemoglobin C (HbC) and alpha-thalassemia. High-performance liquid chromatography (HPLC) procedures and microsequencing were used for characterization of the aminoacid substitution. The main hematological disorder, in relation with the instability of Hb J Guantanamo, seems to be a worsening of the rheological properties of the red blood cells (RBC), as demonstrated by ektacytometric studies. Oxygen-binding properties of the RBC were almost normal, but a slight decrease in cooperativity and lowered Bohr and 2,3-diphosphoglycerate (DPG) effects were observed for pure stripped Hb J Guantanamo. The expression of the electrophoretic charge difference was partly masked, as is often observed when the structural abnormality is situated in or near a contact area.

Amino Acid Sequence↗
PubMed1988

Occurrence of hereditary spherocytosis and beta thalassaemia in the same family: globin chain synthesis and visco diffractometric studies.

Hereditary spherocytosis and beta thalassaemia are rarely inherited together. We have studied a large family of Caucasian extraction in whom these two diseases segregate independently over four generations. The diagnosis rested on specialized laboratory findings and in a number of subjects on the measurement of alpha and beta globin chain synthesis. In addition, a viscometric method (osmotic gradient ektacytometry) was used to evaluate the rheological function of the erythrocytes. In patients inheriting both diseases, the results indicate that the clinical and biological expression of hereditary spherocytosis is modulated by the degree of imbalanced globin chain synthesis. The opposite properties of spherocytes (decreased surface/volume ratio, increased haemoglobin concentration) and thalassaemic red cells (increased surface/volume ratio, decreased haemoglobin concentration) may explain the antagonistic influence of each genotype.

Adolescent↗
PubMed1987

Prenatal diagnosis of hereditary elliptocytosis with molecular defect of spectrin.

Hereditary elliptocytosis (HE) is, in the heterozygous state, a common mild congenital hemolytic disease. In contrast, homozygous elliptocytosis is a severe transfusion-dependent hemolytic anemia. The major determinant of red cell membrane shape and stability is a two-dimensional proteinaceous meshwork named membrane skeleton. Spectrin, the most important protein of the membrane skeleton, is basically a heterodimer composed of alpha and beta chains. Within the membrane, spectrin dimers self-associate to form tetramers. In type I HE spectrin dimer self-association is defective and an excess of spectrin dimer is present in the patient's red cell membranes. The defective self-association is often correlated with an abnormality of the spectrin alpha chain which is depicted by limited tryptic digest of spectrin. In a family previously studied by us (Dhermy et al., 1984), the search for a spectrin defect in the red cells of the fetus of the pregnant mother was indicated for the following reasons: the diagnosis of heterozygous type I HE with the same spectrin variant had been made in the mother as well as in the father. Moreover, homozygous HE had been recognized in one of the children born two years previously with a persistent and severe transfusion dependent hemolytic anemia. Preliminary studies of normal fetal erythrocytes at twenty weeks gestation have shown that fetal and adult spectrin molecules are identical. The results obtained in the fetus at risk allowed us to diagnose type I HE (though elliptocytes were not present in the blood) for the following reasons: (i) erythrocyte deformability was decreased (ii) spectrin self-association was defective with an excess of dimer species in the membrane (iii) limited tryptic digest of spectrin showed the same abnormal pattern as seen in the heterozygous mother, with a decrease in the 80,000-dalton peptide and a concomitant increase in the 74,000-dalton peptide. The heterozygous state, strongly suspected on the tryptic digest pattern of fetal spectrin, was confirmed when the mother gave birth to a baby who did not have hemolytic anemia during the first 18 months of life.

Elliptocytosis, Hereditary↗
PubMed1987

Hereditary pyropoikilocytosis and elliptocytosis in a Caucasian family. Transmission of the same molecular defect in spectrin through three generations with different clinical expression.

Hereditary pyropoikilocytosis (HPP) is a severe hemolytic anemia characterized by a material instability of the red cell membrane leading to cell fragmentation. This fragility may be correlated with functional and structural defects of spectrin. Most HPP patients have been black. We now report three HPP patients from a Caucasian family, the proposita and her two maternal uncles. The proposita's mother and daughter presented mild type I hereditary elliptocytosis (HE), while the proposita's father was clinically and hematologically normal. Our studies revealed a defective ability of spectrin to self-associate, resulting in an excess of spectrin dimer in 4 degrees C extracts in the three HPP patients and to a similar extent in HE relatives. Limited tryptic digestion of spectrin showed a molecular variant in the alpha I domain as expressed by a decreased amount of 80,000-dalton peptide with a concomitant increase in the 74,000-dalton peptide. Investigations in the proposita's father revealed no abnormalities of the erythrocyte membrane. The co-transmission of HPP and HE phenotypes in the same lineage might suggest variability in the clinical expression of the same molecular defect and lead us to discuss the hypothesis of a double heterozygosity in HPP patients.

Adult↗
PubMed1987

Enrichment of blood units with young red cells (neocytes) with the IBM 2991 cell washer.

The transfusion of young red blood cells (neocytes) is a complementary approach to the present treatment of thalassaemia major patients. Fresh neocytes were harvested from 34 volunteers with the IBM 2991 cell washer (CW). The upper part of 24 units was separated into 6 aliquots (T1-T6) of 15 ml each and the residue homogenized. Four biological criteria were used to evaluate young red cell quality, the erythrocyte pyruvate kinase activity, the mean corpuscular volume, the reticulocyte count and ektacytometry; each sample (T1-T6) showed an enrichment with neocytes as compared with the standard unit. A real efficiency of this technique with the IBM 2991 CW was obtained with the first third of the unit, corresponding to the T1-T4 fractions. The estimation of the theoretical mean life span of T1-T2 was 270 days. The last 10 units were separated into two halves: the enrichment of the first half was worse than in the first third of the previous technique. We concluded that the transfusional program of thalassaemia patients could profit by the use of the most enriched part of a standard blood unit with the IBM 2991 CW.

Blood Specimen Collection↗
PubMed1986

Double inheritance of an alpha I/65 spectrin variant in a child with homozygous elliptocytosis.

Hemolytic anemia with red cell fragmentation, poikilocytosis, and elliptocytosis was discovered in a 6-week-old black infant. Both parents and a brother of the propositus had compensated mild Hereditary Elliptocytosis (HE). Elliptocytosis was prominent in the proband's father with the presence of numerous rod-shaped cells whereas, in the proband's mother, elliptocytosis was less marked and cells were less elongated than in the father. The proband's red cells fragmented at 45 degrees C instead of 49 degrees C for control cells. Both the parents' and brother's red cells fragmented at 47 degrees C. The deformability of the proband's red cells was markedly reduced when measured with the ektacytometer; the red cells of both the proband's parent and brother exhibited an intermediate decrease in red cell deformability. Spectrin self-association was defective in the propositus as well as in his parents and brother. Limited tryptic digestion of the proband's spectrin, followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), revealed a complete absence of the normal 80,000 dalton alpha I domain and the presence of an abnormal 65,000 dalton peptide. Two-dimensional isoelectric focusing/SDS-PAGE of limited tryptic digests of spectrin from both the proband's parents and brother revealed a decrease in the normal 80,000 alpha I domain and the presence of the 65,000 peptide variant. On the basis of biochemic studies performed on the patients' spectrin, we concluded that the proband had homozygous HE, having inherited the structural defect of spectrin present in a heterozygous state in each of his parents. On a clinical and morphologic level, homozygous HE imitates two other forms of congenital hemolytic anemia associated with a spectrin self-association defect: HE with pycnocytosis in infancy and Hereditary Pyropoikilocytosis. This report emphasizes the importance of confronting clinical and rheological as well as biochemical investigations in studying and discussing different entities.

Electrophoresis, Polyacrylamide Gel↗
PubMed1985

Pathologic and nonpathologic variants of the spectrin molecule in two black families with hereditary elliptocytosis.

Five patients with hereditary elliptocytosis (HE) from two unrelated black families were studied. The patients had prominent elliptocytosis and a decreased erythrocyte resistance to heat treatment. In one infant blood smears showed elliptocytosis and poikilocytosis; his erythrocytes fagmented at a lower temperature than those of his mother and sister, both having typical mild HE. Defective dimer-dimer association was present in all patients. Limited tryptic digestion of spectrin and subsequent analysis by one- and two-dimensional electrophoresis revealed a similar and reproducible decrease in the 80,000-dalton peptide (alpha I domain) and the concomitant appearance of a 46,000-dalton peptide. All the patients had the polymorphism of the spectrin alpha II domain commonly observed in black populations. In addition, modifications relative to the alpha III domain were detected; similar variants were found in one black control subject out of 136 and are likely related to a genetic polymorphism of the alpha III domain. No differences were observed between the peptide patterns in the infant with poikilocytosis and those of his HE sister and mother.

Adult↗
PubMed1984

Molecular defect of spectrin in the family of a child with congenital hemolytic poikilocytic anemia.

We present the study of a black family in which the proband suffered from a severe neonatal hemolytic anemia with poikilocytosis. Both the parents, sister's, and brother's proband were clinically normal. The presence of poikilocytes in proband led to a search for a red cell membrane skeleton defect. Owing to recent improvements in the erythrocyte membrane knowledge, it is now possible to approach the diagnosis by means of biochemical evaluation of both parents, even if they are asymptomatic. So, the first time discovery of a spectrin self-association defect in both parents allowed us to suspect double inheritance of this abnormality in the proband. A complete morphological and biochemical evaluation of the family allowed us to propound the diagnosis of heterozygous type I hereditary elliptocytosis (HE) for both parents and the sister and the diagnosis of homozygous type I HE for the proband owing to the following reasons: slight ovalocytosis was present in both parents and the sister; cell deformability ektacytometric studies gave the same profiles of curve as those observed in patients with HE. Defective spectrin dimer self-association found in both parents was also observed in the sister and proband, associated with the same abnormal spectrin digest pattern, namely a decrease in the amount of a 80,000-dalton peptide and a corresponding increase in a 74,000-dalton peptide. However, clinical presentation of the proband was consistent either with hereditary pyropoikilocytosis or homozygous hereditary elliptocytosis; erythrocyte thermal sensitivity studies in the proband could not be conclusive because of the presence of transfused cells. Both these diagnoses are discussed in detail.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Hemolytic, Congenital↗
PubMed1983

[Neonatal hemolysis secondary to congenital poikilocytosis].

Hereditary pyropoikilocytosis is a congenital haemolytic anaemia recently described. A new case is reported in which the condition was diagnosed by a study of erythrocyte membrane proteins in the parents. The unusual clinical features of this case lead to a discussion of the relationship between hereditary pyropoikilocytosis and other rare forms of elliptocytosis in children.

Anemia, Hemolytic, Congenital↗