Denaturing high-performance liquid chromatography (DHPLC)-based prenatal diagnosis for tuberous sclerosis

Tuberous sclerosis (TSC) is a frequent autosomal-dominant condition (affecting 1 in 6000 individuals) caused by various mutations in either the hamartin (TSC1) or the tuberin gene (TSC2). This allelic and non-allelic heterogeneity makes genetic counseling and prenatal diagnosis difficult, especially as a significant proportion of TSC cases are due to de novo mutations. For this reason the identification of the disease causing mutation is mandatory for accurate counseling, yet current mutation detection methods such as single-strand conformation polymorphism (SSCP) or denaturing gradient gel electrophoresis (DGGE) are labor intensive with limited detection efficiency. Denaturing high-performance liquid chromatography (DHPLC) is a high-throughput, semi-automated mutation detection system with a reported mutation detection rate close to 100% for PCR fragments of up to 800 bp. We used a recently described DHPLC assay allowing the efficient detection of mutations in TSC1 to analyze the DNA extracted from a chorion villus sample in order to perform a prenatal diagnosis for TSC. The fetus was found not to have inherited the deleterious mutation and the DHPLC diagnosis was confirmed by haplotype analysis. This represents the first DHPLC-based prenatal diagnosis of a genetic disease. Copyright © 2001 John Wiley & Sons, Ltd.     

A fetal cystic neck mass associated with maternal tuberous sclerosis. Case report and literature review

Tuberous sclerosis is a single gene autosomal-dominant disorder, characterized by multiple hamartoma formation. It shows a wide variability of expression. Prenatal diagnosis by means of a DNA or biochemical marker is not yet possible. Ultrasound offers the only way to detect possible antenatal hamartoma formation, which is most commonly found in the central nervous system, the renal system, and the heart. We report a case of fetal involvement that appears unique because of the unusual location of a tumour in the neck of the fetus.     

A new method for spatially moving correlation analysis in geomedicine

A method of correlation analysis within a spatially moving window was applied to two sets of epidemiological/geochemical data in Norway, (1) mortality/disability rates of multiple sclerosis (MS) versus atmospheric fallout of Mg and concentrations of Se in overbank sediment, and (2) incidence rates of malignant melanoma of the skin (MM) versus concentrations of Ca and K in overbank sediment. It appears that n = 17 observation sites within the moving window is a practical compromise between noise in the data at small values of n and a spatial resolution good enough to detect trends in the distribution patterns of the correlation coefficient. For MS versus Mg, MS versus Se and MM versus Ca the correlation coefficients are generally negative and depict systematic distribution patterns with anomalous clusters of sites with good correlation. For MS versus Se the correlation coefficients also form an additional cluster of positive coefficients. Tests with permutated data show that more than 70% of the negative correlation coefficients for MS versus Mg and for MM versus Ca are both significantly different from zero at p<0.05, while less than 15% of those for MS versus Se are significant at the same level. For MM versus K the correlation coefficients are randomly distributed and not significantly different from zero. The described correlations may be effects of confounders and do not per se indicate any causal relationships. However, further research based on these results may well lead to the identification of possible aetiological factors.     

Mercury exposure in sporadic amyotrophic lateral sclerosis patients from Ganga plain region in India: A retrospective study

Amyotrophic lateral sclerosis (ALS), a progressive disorder that usually runs a fatal course within 2–5 years of onset, is characterized by loss of motor neurons in the cortex, brain stem, and spinal cord. In this study mercury (Hg) concentrations were determined in blood samples of 40 ALS patients, of whom 24 ALS patients were from the Ganga plain region and their metal levels were found to be significantly higher. In contrast, Hg levels in the 16 ALS patients from non-Ganga plain regions whose levels were similar to those of the control subjects. Mercury in stream water samples and freshly deposited stream sediment were determined in the locations of patients’ native residences along the Ganga plain region and metal levels were found to be higher than the threshold guideline values for Hg in stream waters recommended by WHO. The geo-accumulation index in selected sites of freshly deposited stream sediment ranged from moderate to highly polluted. The high levels of Hg observed in ALS patients may potentially alter the redox status of neuronal cell components and induce cell-death pathways.     

Prenatal diagnosis of familial tuberous sclerosis following detection of cardiac rhabdomyoma by ultrasound

The authors report a case of tuberous sclerosis (TS), diagnosed by prenatal ultrasound, which was suspected by the detection of intracardiac tumours and confirmed by the family investigation. Cardiac rhabdomyomata can be visualized early on echography and must suggest this diagnosis. The place of genetic counselling and prenatal diagnosis in TS is examined.