A patient with dup(10p)del(8q) and Pendred syndrome

We report on a severely retarded girl with multiple congenital anomalies. Chromosome studies showed a der (8) chromosome with dup(10p) and deficiency for a small distal segment of 8q. Her father proved to be carrier of a de novo balanced translocation between chromosome 8q and 10p. At 1 year the patient was also found to have the Pendred syndrome, an autosomal recessive defect in thyroid organification. The concurrence of chromosome anomalies and single gene disorders might not be too rare, but can be easily overlooked. Yet there are important consequences for genetic counseling. Moreover, recognition of these concurrences may help gene mapping.     

Peripheral nerve stimulation during MRI: Effects of high gradient amplitudes and switching rates

The application of high gradient amplitudes and switching rates for MRI and spectroscopy, resulting in short rise times for the gradient field and high changes of the magnetic flux density in the patient, is known to possibly evoke peripheral nerve stimulation (PNS) in patients. These effects have been studied on 20 volunteers under different experimental circumstances. The results of these measurements are partially in line with earlier findings reported in the literature. New information is found for the dependence of the PNS threshold level as a function of the rise time of the gradient waveform. The PNS threshold level, expressed in terms of dB/dt, is found to be proportional with t^?05, where t is the switch time for the gradients. Indications are found that |B|, the modulus of the gradient vector field, is more closely related to the PNS threshold level than B_z, the imaging component of the gradient field. From the experiments, it is furthermore concluded that only for the imaging protocols characterized by the application of long bipolar repetitive gradient pulse trains, such as echo-planar imaging, PNS is expected at the reported threshold levels. For the protocols based on spin echo, turbo spin echo, inversion recovery, fast field echo, etc., characterized by shorter gradient pulse trains, the threshold levels are expected to be much higher.     

Andrology: Application of different in-situ hybridization detection methods for human sperm analysis

The detection of some types of aneuploidy in human spermatozoacan be based on the use of the fluorescence in-situ hybridizationtechnique (FISH). One of the crucial steps for FISH is to achievea proper decondensation and denaturation of the DNA in the specimen,so as to obtain efficient hybridization results. However, afterDNA decondensation the morphology of sperm heads is partly distortedand the majority of the tails is lost. This situation leadsto problems in the distinction between disomic and diploid spermatozoa,as well as between abnormal spermatozoa and somatic cells. Double-and triple-target FISH can partly solve this discriminationproblem. To improve these procedures we adapted the steps ofdecondensation and visualization of the single sperm cells.Firstly, DNA decondensation with 25 mM dithiothreitol in 1 MTris at pH 9.5 resulted in sperm cells with intact morphologyof both the head and the tail, and allowed efficient single-,double- and triple-target ISH to be performed. Secondly, weapplied a novel detection method, based on enzyme immunocyto-chemicalreactions, with coloured precipitation products. Thirdly, thisISH procedure was combined with Diff-Quik staining and bright-fieldmicroscopy. This absorption method has the advantage of a permanentsignal, and the adapted cytoplasmic staining of the sperm plasmamembrane allows the visualization of the outline of the singlespermatozoon. Using this approach, therefore, it is possibleto discriminate between disomic, diploid and abnormal spermatozoa,somatic cells and spermatozoa that overlap, because the morphologyof the cells is not distorted and the tails of the spermatozoaare intact and properly visualized.     

Recurrence of nephrocalcinosis after renal transplantation in an adult patient with primary hyperoxaluria type I

The medical history of a 42-year-old patient with primary hyperoxaluria type I is presented. Primary hyperoxaluria was suspected after renal transplantation, when oxalate deposits were found in a biopsy of the kidney graft. Diagnosis of type I hyperoxaluria was confirmed by the finding that significantly increased amounts of glycolic acid and oxalic acid were excreted. Treatment of the patient with 500 mg pyridoxine daily resulted in a decrease of the excretion of oxalate to normal values.     

Anticipation resulting in elimination of the myotonic dystrophy gene: a follow up study of one extended family.

We have re-examined an extended myotonic dystrophy (DM) family, previously described in 1955, in order to study the long term effects of anticipation in DM and in particular the implications for families affected by this disease. This follow up study provides data on 35 gene carriers and 46 asymptomatic at risk family members in five generations. Clinical anticipation, defined as the cascade of mild, adult, childhood, or congenital disease in subsequent generations, appeared to be a relentless process, occurring in all affected branches of the family. The cascade was found to proceed asynchronously in the different branches, mainly because of an unequal number of generations with mild disease. The transition from the mild to the adult type was associated with transmission through a male parent. Stable transmission of the asymptomatic/mild phenotype showed a female transmission bias. We further examined the extent and causes of gene loss in this pedigree. Gene loss in the patient group was complete, owing to infertility of the male patients with adult onset disease and the fact that mentally retarded patients did not procreate. Out of the 46 at risk subjects in the two youngest generations, only one was found to have a full mutation. This is the only subject who may transmit the gene to the sixth generation. No protomutation carriers were found in the fourth and fifth generations. Therefore it is highly probable that the DM gene will be eliminated from this pedigree within one generation. The high population frequency of DM can at present not be explained by the contribution of asymptomatic cases in the younger generations of known families, but is probably caused by the events in the ancestral generations.     

Decreased human semen quality and organochlorine compounds in blood

BACKGROUND: Various studies have been performed in which potential effects of xenoestrogens on fertility or sperm parameters were investigated by comparing groups of subjects exposed to different levels of these chemicals. METHODS: In our study we used an alternative approach, as we selected one group of men with very poor semen quality and another group with normal semen quality and determined the blood organochlorine contents in order to determine whether a difference in these levels could be established. Organochlorine compounds, including polychlorinated biphenyls (PCB) and PCB metabolites, were detected using gas chromatography. The concentrations were compared between both groups, and related to semen parameters. RESULTS: A comparison of both groups did not reveal significant differences in organochlorine levels. Linear relationships were found when PCB and metabolite concentrations were related to the age of the volunteers. Focusing on the subgroup of men with normal semen quality showed that sperm count and sperm progressive motility were inversely related to the concentrations of PCB metabolites within this group. CONCLUSIONS: The finding of a significantly decreased sperm count in relation to an elevated PCB metabolite level within the subgroup of men with normal semen quality is important. This is the first time that a correlation between exposure to environmental pollutants with endocrine-disrupting capacity and human sperm quality has been observed.     

Segregation analysis of a translocation (16;21)(p11;q22) in a large pedigree

A large family with an inherited reciprocal translocation (16;21) is described. An unbalanced karyotype due to adjacent-1 segregation was documented in 6 cases, whereas 25 children dying within the first year of life and 4 individuals dying at later ages probably had the same abnormality. Therefore minimal and maximal risk estimates were calculated to be 6.0% and 26.5% for female, respectively, 4.8% and 33.3% for male translocation heterozygotes. Among the karyotyped phenotypically normal offspring of male as well as female carriers the ratio of normal children to balanced carriers was not different from 1:1.     

Assessing future trends in indoor air quality

Several national and international health organizations have derived concentration levels below which adverse effects on men are not expected or levels below which the excess risk for individuals is less than a specified value. For every priority pollutant indoor concentrations below this limit are considered "healthy." The percentage of Dutch homes exceeding such a limit is taken as a measure of indoor air quality for that component. The present and future indoor air quality of the Dutch housing stock is described for fourteen air pollutants. The highest percentages are scored by radon, environmental tobacco smoke, nitrogen dioxide from unvented combustion, and the potential presence of housedust mite and mould allergen in damp houses. Although the trend for all priority pollutants is downward the most serious ones remain high in the coming decades if no additional measures will be instituted.