Familial renal glucosuria (FRG) is an inherited renal tubular disorder characterized by persistent isolated glucosuria in the absence of hyperglycemia. Mutations in the sodium/glucose co-transporter SGLT2 coding gene, SLC5A2, were recently found to be responsible for the disorder. Here, we report the molecular and phenotype study of five unrelated FRG families. Five patients were identified and their family members screened for glucosuria. SLC5A2 coding region of index cases was polymerase chain reaction amplified and sequenced. Five different mutations are reported, including four novel alleles. The IVS12+1G>A and p.A102V alleles were identified in homozygosity in index patients of two unrelated families. A proband from another family was compound heterozygous for the p.R132H and p.A219T mutations, and the heterozygous p.Q167fsX186 frameshift allele was the only mutation detected in the affected individual from an additional pedigree. For the remaining family no mutations were detected. The patient homozygous for the p.A102V mutation had glucosuria of 65.6 g/1.73 m(2)/24 h, evidence of renal sodium wasting, mild volume depletion, and raised basal plasma renin and serum aldosterone levels. Our findings confirm previous observations that in FRG, transmitted as a codominant trait with incomplete penetrance, most mutations are private. In the only patient with massive glucosuria in our cohort there was evidence evocative of renin-angiotensin aldosterone system activation by extracellular volume depletion induced by natriuresis. Definite proof of renin-angiotensin aldosterone system activation in FGR should rely on evaluation of additional patients with massive glucosuria.

The effect of α-adrenergic, β-adrenergic, and combined blockade on the increase in plasma renin activity produced by renal nerve stimulation was studied in dogs. Prior treatment with the blocking agent propranolol abolished this response. In dogs given phenoxybenzamine, blood pressure fell and plasma renin activity rose, but in dogs given propranolol as well as phenoxybenzamine the same depressor response was observed without a rise in plasma renin activity. Stimulation of the renal nerves in dogs treated with phenoxybenzamine caused a further increase in plasma renin activity, while no increase was observed in dogs that had received both blocking agents. The data are consistent with the hypothesis that renal nerve stimulation and α-adrenergic blockade increase renin secretion by way of a β-adrenergic receptor. Renal nerve stimulation also increased systolic and diastolic blood pressure. This pressor response was unaffected by β-adrenergic blockade, but was reduced by α-adrenergic blockade.

Smith-Lemli-Opitz (RSH) syndrome (SLOS, OMIM 270400) is a relatively common, autosomal recessive disorder of cholesterol biosynthesis with a broad spectrum of phenotypic abnormalities caused by mutations of the 7-dehydrocholesterol reductase gene (DHCR7) on chromosome 11. Prenatal diagnosis can be established by detection of elevated 7-dehydrocholesterol or of SLOS-causing mutations in the DHCR7 gene. We report here our experience with molecular prenatal diagnosis of SLOS. Mutation analysis of the DHCR7 gene was performed in chorionic villus samples of 13 pregnancies of couples with a family history of SLOS and known SLOS genotypes. This approach is accurate and reliable. If facilities for biochemical analysis are not available, or in cases with ambiguous biochemical patterns, molecular prenatal diagnosis is an attractive, alternative option.

The Smith-Lemli-Opitz syndrome (SLOS), or RSH syndrome, is a well-characterized multiple congenital anomalies/mental retardation syndrome. The phenotype has been redefined to include mildly affected individuals with minor anomalies and developmental delay, and severe malformations with pre- and perinatal mortality. The condition is due to the deficient activity of the enzyme 7-dehydrocholesterol (7-DHC) reductase [Shefer et al., 1995: J Clin Invest 96:1779-1785], and the gene has been mapped to chromosome 11q13 [Moebius et al., 1998: Proc Natl Acad Sci USA 95:1899-1902]. We describe here a consanguineous family of Syrian-Lebanese ancestry with three sibs affected with SLOS: two with a mild variant, while the other had severe disease and died in the first year of life. Mutation analysis demonstrated a novel mutation in the DHCR7 gene, present in homozygous form in the two affected individuals available for testing, and heterozygous in the parents. The wide intrafamilial variation of clinical severity in these three sibs is an important finding in SLOS.

We report on a woman with Muellerian aplasia, renal and skeletal anomalies, and minor dysmorphic signs. Conventional cytogenetic analysis revealed mosaicism for a small supernumerary, undefinable ring chromosome. Chromosome microdissection and reverse painting demonstrated that this marker contained pericentric material from chromosome 8 (8p12q12). Thus, we identified a Muellerian aplasia phenotype with partial trisomy 8 mosaicism.

The optimal risk cutoff value was 0.003 with sensitivity 80.0% (28.4-99.5), specificity 91.7% (89.5-93.5), positive likelihood ratio 9.6 (5.8-15.8), and negative likelihood ratio 0.2 (0.04-1.3). The risk cutoff value of which the sensitivity was 100% was 0.00065. Conclusions: A simple and traditional method of calculating the risk of DS using maternal age and NT thickness may be acceptable to screen DS in triplet pregnancy.

Virtual poster abstractsResults: Fetal tymus volume found to be significantly lower in patients with IUGR compared to those without complications. When the fetal tymus volume measured using the VOCAL program was used as a marker for development of IUGR, a threshold of 0.1645 had 89.5% sensitivity and 50% specificity (AUC 0,789, p = 0,019, 95% CI 0.649-0.930). According to the results of the binary logistic regression analysis, the parameter of fetal tymus volume measured at 15-24 weeks can be used as a predictive factor for the development of IUGR(p = 0.041). Conclusions:The results of this study demonstrated that it is possible to predict the development of IUGR by adding tymus volume measurement to the second trimester screening parameters. Thus, identification of patient groups at risk will enable close monitoring of these pregnant women and thereby ensure a reduction in fetal morbidity and mortality caused by IUGR. VP42.03The role of ductus venosus blood flow velocities in first and second trimester of pregnancy in prediction of the fetal and neonatal condition

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