Erythrocyte antioxidant system in Down syndrome.

It has been emphasized that an increased oxidative damage can exist in Down syndrome (DS), and that superoxide dismutase (SOD-1) seems to play a role in the pathogenesis of this disorder. We have studied the antioxidant system SOD-1, catalase, glutathione peroxidase (GSH-Px) and reduced glutathione (GSH) in erythrocytes of DS adults in order to evaluate if these cells are protected against oxidant stress. SOD-1 and GSH-Px were significantly increased while catalase and GSH activities were normal. These results suggest that the erythrocytes of these individuals have an unbalanced antioxidant system which may participate in the manifestations of DS.

Polymorphism of the locus CHE1 of pseudocholinesterase in Italy.

A sample of the Italian population was investigated to determine the CHE1*u, CHE1*a and CHE1*f allelic variants at the polymorphic locus CHE1 for the serum cholinesterase enzyme. We examined 4051 serum samples from schoolchildren of Milan and estimated the following allelic frequencies for the CHE1 locus: CHE1*u = 0.9636; CHE1*a = 0.0263; CHE1*f = 0.0101. These allelic frequencies are compared with those from other Italian, European, North African and Middle-Eastern countries. Our study confirms the validity of Garry's method in discriminating between the "usual" genotype and the "atypical" and "fluoride-resistant" ones.

[Bilateral familial anophthalmos]. / Anophtalmie bilatérale familiale.

In the examined family the proband, a 14 months old male, presented a bilateral anophthalmos, bilateral cryptorchism, phimosis and decalcification of the nails. The palpebral fissures and the eyelids are smaller than normal; the orbit was empty, clad by a connective tissue without ocular buds. The testicles are unpalpable in the inguinal canal. The proband have a normal karyotype. Also a brother of the proband, dead for meningitis (age five months), had bilateral anophthalmos. The maternal branch of the family is lacking in hereditary pathology. On the contrary, the anamnesis of the paternal branch present very interesting data. His grandmother married twice; from the first marriage came, at the second generation, the sibship of the father, who had a sister with Franceschetti syndrome and another sister with double lower dental arch. From a second marriage originated, at the second generation, eleven siblings sibship, all seriously malformed and a dead infant, but the first-born having bilateral anophthalmos.

[Ectodermal dysplasia with severe odontodysplasia. Study of an affected family]. / Dysplasie ectodermique avec odonto-dysplasie grave. Etude d'une famille atteinte.

We present a very extensive family tree, who includes six generations and 17 women and 9 males affected by ectodermal Dysplasia. The clinical symptomatology is more serious in the males than in the females. In our family the syndrome manifests a segregation that suggests a semi-dominant X-linked heredity.

Antioxidant system and serum trace elements in alpha-thalassaemia and Hb Lepore trait.

Erythrocyte antioxidant enzymes, superoxide dismutase, catalase and glutathione peroxidase were found to be significantly high in subjects with alpha-thalassaemia and Hb Lepore trait, as a consequence of the increased oxidant stress which is known to exist in these conditions. Among the serum trace elements present in these enzymes, selenium was increased in subjects with Hb Lepore trait and significantly low in those with alpha-thalassaemia trait, while selenium erythrocyte content was significantly increased in alpha-thalassaemic subjects.

[Clinical and genetic study of a family with hereditary essential myoclonus]. / Etude clinique et génétique d'une famille atteinte de myoclonus essentiel héréditaire.

A large family with essential hereditary myoclonus is reported. Symptoms and signs, the age of clinical onset and the evolution are presented. The disease is autosomal dominant with complete penetrance.

[A family with the EEC syndrome (ectrodactily, ectodermal dysplasia clefting syndrome): clinical variability and genetic counseling]. / Une famille atteinte de EEC-syndrome (ectrodactily ectodermal-dysplasia clefting syndrome): variabilité clinique et conseil génétique.

In a family with segregation of EEC-Syndrome we observed five children--two girls and three males--(two of them dizygotic twins) affected by very various phenotypes of the syndrome. The ocular symptomatology was represented by agenesis or stenosis of lacrimal ducts: two children were operated, the other suffered from frequent inflammations. The study of the family suggest an autosomic dominant heredity with defect of penetrance on the father.

Relationship of the phenotypic expression of the A-IMilano apoprotein with plasma lipid and lipoprotein patterns.

The plasma lipoprotein and apolipoprotein profile of 29 adult A-IMilano (A-IM) carriers and 29 age- and sex-matched non-affected subjects of the same kindred was examined, in order to investigate linkages between the lipid and apoprotein abnormalities and the phenotypic expression of the biochemical disorder. Carriers (A-IM+) showed a higher prevalence of hypertriglyceridemia (12 out of 29); they also had lower plasma total cholesterol, esterified cholesterol and phospholipids, compared to non-carriers. Lipoproteins were characterized by a significant enrichment of triglycerides in low and high density fractions (LDL and HDL), and by the expected striking reduction of HDL mass and cholesterolemia. Conversely, no significant alterations of the major circulating apolipoprotein levels, except for apo A-I and apo A-II, were noted in the A-IM+. The increased free cholesterol/esterified cholesterol ratio in plasma (most marked in HDL), was accompanied by a significant reduction of the lecithin cholesterol acyl transferase molar activity. Several correlations pertaining to lipids, lipoproteins and apoproteins were examined: cholesterol and triglycerides in HDL and, more remarkably, apoprotein A-I and C-III levels in plasma were significantly correlated in the A-IM+. While there was no significant prevalence of specific apo E phenotypes, plasma triglycerides and apo C-II levels were highly correlated in the carriers. The A-IM subjects, while in the presence of severe lipoprotein risk factors, may have alternative mechanisms of cholesterol disposal, potentially responsible for the apparently low prevalence of atherosclerosis.

AIMilano apoprotein identification of the complete kindred and evidence of a dominant genetic transmission.

The AIMilano apoprotein variant is associated with a marked reduction of high density lipoprotein (HDL) cholesterol levels and with increased triglyceridemia. In spite of the low HDL-cholesterol (HDL-Ch), carriers do not generally show clinical signs of atherosclerosis. The biochemical disorder is linked to a molecular change in apoprotein AI, that is, an arg----cys substitution in the 173 position, thus allowing the formation of AIMilano-AIMilano dimers and AIMilano-AII complexes. The origin of the variant gene has been located in Limone sul Garda, a small community in Northern Italy (about 1,000 individuals). This community has a genetic, biochemical, and clinical individuality, consequent to its isolation up to a few years ago; the citizens show highly uniform alimentary habits and elevated consanguinity. The complete population of the small village was sampled, and, by the use of an analytical isoelectric focusing technique for the detection of the mutant, a total of 33 living carriers, ranging in age from 2 to 81 yrs, were identified. Analysis of the genealogic tree of the complete family groups showed that the apoprotein (apo) AIMilano is transmitted as an autosomal dominant trait, all carriers coming from a single mating couple, living in the eighteenth century. The carriers are heterozygous for the apoprotein variant.

Familial associations of lipids and lipoproteins in a highly consanguineous population: the Limone sul Garda study.

The impact of genetic factors on the levels of plasma lipids and lipoproteins was evaluated in the total population of a small village. Limone sul Garda, separated up to recent years from neighboring communities, shows a high degree of consanguineity: major blood group phenotypes differ from nearby provinces for at least three gene frequencies. The absence of a difference in plasma lipid correlations between parent-pediatric offspring and parent-adult offspring, is consistent with the uniformity of living habits in the Limone community. Correlation coefficients proved highly significant only for plasma total cholesterol (range of r: 0.223 to 0.359). Differently from other reports, correlations for low density and high density cholesterolemias (LDL and HDL-C) were mostly nonsignificant in the parent-offspring comparisons. Similarly, only intersibling correlations for triglycerides (TG) were statistically significant. As indicated in other genetic studies on plasma lipoprotein levels (also in the Limone sul Garda study), TG and HDL-C were negatively correlated, whereas the correlation was positive between TG and LDL-C levels. The examined population does not, therefore, show a metabolic behavior at variance from other investigated groups. This study, offering a unique opportunity for enucleating genetic from environmental factors, suggests that most familial clusterings of lipoprotein concentrations are environmentally determined, whereas total cholesterolemia is controlled by autosomal mechanisms, without significant variations between sexes.

[Detection of microcythemia in a school population in Milan: survey of microcythemic subjects 8 years after the diagnosis was made]. / Dépistage de la microcytémie dans la population scolaire de Milan: enquête portant sur les microcytémiques 8 ans après l'établissement du diagnostic.

In the Milan School population the screening for microcythemy is performed from 1963. It was conducted an investigation among the subjects who were recognized microcythemics eight years ago and who now are eighteen years old. Almost all of them are conscious about their situation and about half of them has a scrupulous notion about a cross-breeding with a high risk. Are also offered the results of the research on the personal behaviour in front of the direct prevention of the mediterranean anemia by prenatal diagnosis.

Erythrocyte glutathione peroxidase in subjects of Mediterranean origin. A family study.

Erythrocyte glutathione peroxidase (GSH-Px) was assayed in subjects of Mediterranean origin and the distribution of the data obtained seems to confirm the existence of two alleles coding for low and high enzyme activity. In order to define the limits of expected genotypes less arbitrarily we studied families where parents' genotypes could allow us to define that of the children. Gene frequencies were calculated from genotype frequencies of an unrelated population and from crossings distribution by the Hardy-Weinberg equation. We observed a good agreement between gene frequencies obtained by these two different methods.

[Glucose-6-phosphate dehydrogenase deficiency among the student population of Milan]. / Le déficit en glucose-6-phosphate deshydrogénase dans la population scolaire de Milan.

In our Department a yearly screening is carried out on the school population of Milan, in order to detect beta-thalassaemic trait carriers and G-6-P-D deficient males. This report deals with the results obtained on a group of 21,118 males. They all showed very low enzyme activity and often just detectable; the fall of GSH after incubation with acetylphenhylhidrazine appeared significantly greater than normal. Only 3 cases of hemolytic crises by fava beans ingestion and 7 cases of neonatal jaundice resulted from anamnestic data.

[Prenatal diagnosis of a case of familial recurrence of unilateral diaphragmatic agenesis]. / Diagnostic prénatal d'un cas de répétition familiale d'agénésie unilatérale du diaphragme.

Prenatal diagnosis of different fetal malformations have been performed by echography. The authors report a case of recurrence of monolateral diaphragmatic agenesy in sibs. The diagnosis was achieved at the 23 degrees week of gestation. Some methodological details are also proposed to improve the possibility of early diagnosis. Embryological and epidemiological data have been evaluated.

Antioxidant system in sickle red cells.

Erythrocytes containing abnormal haemoglobins with high affinity for red cell membrane are subjected to enhanced oxidant stress. Since HbS is known to have high affinity for red cell membrane and sickle cells are particularly susceptible to membrane lipid peroxidation, the behaviour of erythrocyte antioxidant system has been evaluated in 20 subjects, heterozygous for sickle cell anaemia. These subjects have shown normal levels of reduced glutathione, increased superoxide dismutase and glutathione peroxidase activities and low catalase activity. These data suggest that such an unbalanced antioxidant system can not prevent damage by the enhanced production of oxygen free radicals by membrane-bound HbS molecules.

Erythrocyte superoxide dismutase, catalase and glutathione peroxidase in glucose-6-phosphate dehydrogenase deficiency.

Glucose-6-phosphate dehydrogenase (G-6-PD) deficient erythrocytes are particularly sensitive to oxidant stress. In order to evaluate if these cells are protected against oxidant damage, we assayed the antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) in erythrocytes of G-6-PD deficient (hemizygous and heterozygous) subjects. Normal levels of antioxidant enzymes were found in all subjects examined both with positive and negative histories of haemolytic crisis after fava bean or drug ingestion. In contrast, high levels of catalase and GSH-Px were found in a small group of G-6-PD deficient subjects (hemizygous and heterozygous) with beta-thalassaemia trait, probably by reason of the chronically enhanced oxidant stress which is present in beta-thalassaemia.