Prenatal diagnosis and intrafamilial clinical heterogeneity of Fraser syndrome

Fraser syndrome (MIM 219000) is a rare disorder of autosomal recessive inheritance, characterized by the association of cryptophthalmos, syndactyly and genital abnormalities. Here we report on two cases of Fraser syndrome (cryptophthalmos syndrome) in a non-consanguineous couple, with variable expression in echographic, clinical and autopsy findings. Furthermore, we highlight the difficulties in prenatal diagnosis of Fraser syndrome. Copyright © 2002 John Wiley & Sons, Ltd.     

Prenatal diagnosis of Juberg–Hayward syndrome

Juberg–Hayward syndrome is a rare autosomal recessive syndrome characterised by the association of growth retardation, microcephaly, cleft lip and palate, and thumb and radial ray abnormalities. To date, no prenatal cases have been reported. Here, we report on the first prenatal case of Juberg–Hayward syndrome. The diagnosis was established following fetopathological study. Besides the cardinal features of the syndrome, this prenatal case was remarkable for the severity of the short arm malformation and by the finding of big toe agenesis and cerebral abnormalities including hydrocephalus, agenesis of corpus callosum, and cerebellar hypoplasia. We conclude that the diagnosis of Juberg–Hayward syndrome can be discussed prenatally following ultrasound diagnosis of the association of intrauterine growth restriction, microcephaly, thumb/radial anomalies, and cleft lip/palate. Copyright © 2005 John Wiley & Sons, Ltd.     

A Variance Estimator for Constrained Estimates of Change in Relative Categorical Frequencies

Consistent estimators of change and state becomes an issue when sample data come from a mix of permanent and temporary observation units. A joint maximum likelihood estimator of state and change creates estimates of state that depend on antecedent viz. posterior survey results and may differ from estimates of state derived from a single-date analysis of the sample data. A constrained estimator of change in relative categorical frequencies that eliminates this potential inconsistency is proposed and a model based estimator of their sampling variance is developed. The performance of the constrained estimator is quantified against six criteria and a joint maximum likelihood estimator in simulated sampling from 15 populations with three combinations of permanent and temporary samples, four to six categorical class attributes, and constant size between sampling dates. Bias of the constrained estimators was negligible but larger than for joint maximum likelihood estimators. Mean absolute deviations and variances of constrained estimators were generally at par with the joint estimators. Constrained estimators of root mean square errors and achieved coverage of nominal confidence intervals of constrained estimators were occasionally better. A generalized variance function for the constrained estimates of change is provided as a computational shortcut.     

Measurements of fractionated gaseous mercury concentrations over northwestern and central Europe, 1995-99

Although it makes up only a few per cent. of total gaseous mercury (TGM) in the atmosphere, the fraction of oxidised (divalent) mercury plays a major role in the biogeochemical cycle of mercury due to its high affinity for water and surfaces. Quantitative knowledge of this fraction present in mixing ratios in the parts-per-10(15) (ppq) range is currently very scarce. This work is based on approximately 220 data for divalent gaseous mercury (DGM) collected during 1995-99 in ambient air. Over the course of the measurements, the sampling and analytical methods were modified and improved. This is described here in detail and includes transition from wet leaching and reduction procedures to thermo-reductive desorption, the use of annular as well as tubular denuders and adoption of an automated sampling system. The concentration of DGM exhibited a strong seasonal behaviour in contrast to atomic gaseous mercury, with low values in winter and maximum values in summer. The DGM/TGM ratios were frequently found to be below the detection limit (< or = 1%) and in the range 1-5%. A trend of diurnal DGM patterns was observed and implies photolytically induced sources. Scavenging of DGM during rain events was also noticed.     

Successful DNA-based prenatal exclusion of juvenile neuronal ceroid lipofuscinosis

A family with two siblings, 10 and 8 years old, both with clinical and ultrastructural evidence of juvenile neuronal ceroid lipofuscinosis is described. The family was found to be informative for the restriction fragment length polymorphisms (RFLPs) detected by the probes pCJ52–95Ml (locus D16S148) and pCJ52-94Tl (locus D16S159) flanking the juvenile neuronal ceroid lipofuscinosis locus, CLN3. The parents were both heterozygous using these probes, while their two children with juvenile neuronal ceroid lipofuscinosis were both homozygous. Chorionic villi analysis showed that the fetus was heterozygous and had inherited the one allele of the mother which was not found in the two siblings. This suggested that the fetus had derived one healthy allele from the mother, the risk for a double crossing-over being less than 1 per cent. Electron microscopy showed no fingerprint inclusions in chorionic villi. The child was investigated at 6 months of age and found to be healthy, as new fingerprint inclusions were found at electron microscopy and no vacuolated lymphocytes were found in the blood smear. Due to the risk of heterogeneity, both DNA-based analysis and electron microscopy on chorionic villi are recommended for prenatal examination for juvenile neuronal ceroid lipofuscinosis.