[Genetic study of holoprosencephaly]. / Etude génétique de l'holoprosencéphalie.

Holoprosencephaly (1/16,000 live births; 1/250 conceptuses) is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, affecting both the forebrain and the face. Clinical expressivity is variable, ranging from a single cerebral ventricule and cyclopia to clinically unaffected carriers in familial dominant autosomic holoprosencephaly. The disease is genetically heterogeneous but additional environmental agents also contribute to the aetiology of holoprosencephaly. In our cohort of 143 patients, 28 heterozygous mutations were identified: 15 in the Sonic hedgehog gene (SHH), 6 in ZIC2, 5 in SIX3, and 2 in TGIF. Functional tests have been set up to validate the significance of SHH amino acids replacements. Novel phenotypes associated with a mutation have been described such as abnormalities of the pituitary gland and corpus callosum, colobomatous microphthalmia, choanal aperture stenosis and isolated cleft lip. This study confirms the great genetic heterogeneity of the disease, the important phenotypic variability in holoprosencephalic families, and the absence of evident genotype-phenotype correlations.

Serum paraoxonase activity and paraoxonase gene polymorphism in type 2 diabetic patients with or without vascular complications.

BACKGROUND: Serum paraoxonase (PON) activity and the relevance of PON gene polymorphism in vascular complications of type 2 diabetic patients were investigated in a case-control study. METHODS: The population included 105 control subjects, 96 diabetic patients without vascular complications and 71 diabetics with vascular complications. RESULTS: Serum PON activity was significantly decreased (p<0.001) in diabetic patients without vascular complications: 207 IU (25-817) compared with the controls: 259 IU (24-950). Although serum PON activity was also decreased: 232 IU (34-797) in the population with vascular complications, the difference was not statistically significant (p=0.11). The Q192 allele frequency is significantly higher (p<0.005) in diabetics without vascular complications (77%), and with vascular complications (73%) than in the controls (63%). No significant association was found between either PON(1)55 L/M and PON(2)311 C/S gene polymorphisms and vascular complications. CONCLUSIONS: The difference in allele frequency for the PON(1) Q/R 192 gene polymorphism may be the cause of the low paraoxonase activity observed in type 2 diabetes mellitus. Further studies need to be conducted to elucidate the role of the enzyme in the development of vascular complications in diabetes.

Determination of lipoprotein(a) concentrations and apolipoprotein(a) molecular weights in diabetic patients.

Lipoprotein(a) (Lp(a)) with atherogenic and thrombotic properties has been frequently studied in diabetes, because a high cardiovascular risk has been reported both in type 1 and type 2 diabetes. Few studies have considered genetic factors, especially the isoforms of apolipoprotein(a). The aim of this work is to determine the distribution of apo(a) phenotypes in the serum of 148 diabetic patients (59 type 1, 89 type 2) with or without vascular complications. Apo(a) phenotypes are determined using 4-15% sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by immunoblotting (PhastSystem - Pharmacia). An inverse relationship is observed between Lp(a) serum concentration and the apparent molecular mass of apo(a) isoforms: type 1 r=- 0.61, p<0.01; type 2 r=- 0.55, p<0.01. The frequency of apo(a) isoforms is significantly different between type 1 and type 2 diabetes mellitus. A higher prevalence of isoforms of low molecular weight was observed in the type 2 diabetic population.

Fortuitous diagnosis of the association of hemoglobin J-Broussais with beta + thalassemia.

The authors report a case, not described so far in literature, of an association of HbJ-Broussais [alpha (90 (PG2) lys-->asn beta 2] with beta + thalassemia in a young girl born of Italian father and Breton mother. This association is clinically silent. Biochemistry revealed, besides HbA, the presence of HbJ-Broussais in the proportion of 19.4% and HbA2 value of 3.9%. These percentages, slightly lower than expected, are explained. A familial study is presented.

Serum lipid, apolipoprotein and lipoparticle levels in the human fetus.

Blood collected from 62 fetuses aged 20-38 weeks of gestation was studied. The values of ten lipid parameters were determined: cholesterol (TC), triglycerides (TGs), apolipoprotein A1 (apo A1), apolipoprotein B (apo B), apolipoprotein E (apo E), total apolipoprotein CIII (apo CIII), apolipoprotein CIII present in particles containing apo B (apo CIII LpB) or not (apo CIII Lp non-B), lipoparticles A1 (LpA1), and lipoprotein a (Lp(a)). The results show that, except for apo E, all the studied parameters were present in lower concentrations than in adults and newborns, and that Lp(a) is not detectable at that stage in life.

[Isolation and physico-chemical properties of rat ceruloplasmin]. / Isolement et propriétés physico-chimiques de la céruloplasmine de rat.

Ceruloplasmin was isolated from inflammatory rat serum after two chromatographies, employing column chromatography with D.E.A.E. cellulose and Sephadex G 200, and after electrophoresis. The determination of phys'co chemical constants allows to compare the human ceruloplasmin.

[Relation between ceruloplasmin and vitamin A in Sprague-Dawley rats]. / Relation entre céruloplasmine et vitamine A chez le rat de souche Sprague-Dawley.

The Moore's hypothesis concerning a relationship between the metabolism of copper and that of vitamin A led us to consider a possible relationship between this vitamin and ceruloplasmin, the carrier protein for copper. Experiments were carried out on Sprague-Dawley rats. The ceruloplasmin level of control animals and vitamin A - deficient rats was determined An average increase between 22 and 33% was observed in the animals with vitamin A deficiency, the highest levels being observed in the females. These results are in agreement with Peterson's previous work. A second type of experiment was carried out to confirm these results. The rats were raised in a copper-deficient diet and the vitamin A level was regularly determined. In these conditions serum and liver levels of vitamin A are normal and do not vary, ceruloplasmin level is zero; however apoceruloplasmin is still being synthetized : Nevertheless at the ultime state of the deficiency vitamin A level decreases while apoceruloplasmin increases. These results raise the following question. Could the relationship between ceruloplasmin and vitamin A be possibly due to an inflammatory state in vitamin A deficient rats. In this respect a third series of experiments were undertaken and are in progress; the vitamin A and ceruloplasmin levels are regularly determined.