Genome-wide androgenetic mosaicism.

Individuals with mosaic paternal uniparental disomy (UPD) of apparently all chromosomes have recently been described. They show a 46,XX karyotype, but with a mixture of normal biparental cells and cells entirely of paternal isodisomic origin. We describe an infant who primarily showed signs of Beckwith-Wiedemann syndrome (BWS), but also had other severe and eventually lethal medical problems, notably refractory hypoglycemia. We performed methylation studies for BWS, but incidentally for Angelman syndrome (AS) on leukocytes and in a skin FFPE sample. We also performed chromosome microarray [CNV and single-nucleotide polymorphism (SNP) array] on leukocytes. We found that the patient had hypomethylation consistent with both BWS and AS. Remarkably, this was due to mosaic paternal UPD for chromosomes 11 and 15, respectively. The SNP microarray showed mosaic paternal UPD for all chromosomes. Patients with unusual phenotypes for a typical imprinting disorder should be studied further with assays for imprinted loci on other chromosomes. Chromosomal SNP microarrays are useful in identifying patients with multiple UPDs, sometimes of the whole genome.

Trisomy 8 is a characteristic finding in pleuropulmonary blastoma.

The cytogenetic findings in pleuropulmonary blastoma (PPB) have not been widely studied and reported and are of interest in view of the implications that PPB has for additional tumors in the patient and the patient's relatives. Using standard tumor cytogenetic methodology, we investigated three cases of PPB encountered in our institution over a 5-year period. Trisomy 8 was the only karyotypic abnormality in a localized type 2 PPB and was present with other abnormalities in another type 2 PPB and a massive type 3 PPB. Review of the literature yielded three additional karyotyped PPBs; all had trisomy 8 as part of the abnormalities detected. Trisomy 8 appears to be a characteristic of PPB and may be related to the development of PPB and related tumors.

Keeping mum.

It takes patience and persistence to extract information from hospitals about their maternity care, as Jane Waterson discovered in her attempts to get answers from hospitals in Northern Ireland.

TCK: a clinical genetics data collection system.

This work examines the database design and user interface design for a clinical genetics data collection system known as TCK. A specific design goal is automatic generation of the CORN reports. Emphasis in this paper is on how the logical data model resulting from the database design, and the user interface work together to enforce the enterprise results pertaining to data. Data screens are shown, sample queries are explained and the data mapping to the CORN reports presented.

Providing services for women with difficulties with alcohol or other drugs: the current U.K. situation as seen by women practitioners researchers and policy makers in the field.

This exploratory paper reports on the current U.K. situation of service provision as seen by women practitioners, researchers and policy makers working in the area. Most agencies represented offered particular facilities for women: women-only groups, women workers and women-focussed research. Voluntary agencies were more likely to make provision than statutory agencies. The lack of childcare facilities and public stigmatization of women with addiction problems were commonly encountered problems. The study emphasised the need to develop a more adequate theoretical understanding of the area and for more specific literature on the problem to be more widely available.

A recessive form of congenital contractures and torticollis associated with malignant hyperthermia.

Two families are presented, each with two affected sibs, all four of whom seem to have a newly described and specific form of congenital contractures (arthrogryposis). The affected subjects have congenital torticollis, dysmorphic, asymmetrical, myopathic facial features, and progressive scoliosis. Two sibs had cleft palate. Malignant hyperthermia has occurred in two of the patients.

Detection of neural tube defects with alpha-fetoprotein measurement in amniotic fluid. A protocol for managing elevated values.

The clinical efficacy of rocket immunoelectrophoresis (RIE) and radioimmunoassay (RIA) methods for the measurement of amniotic fluid alpha-fetoprotein (AFP) were compared in separate series of over 1,000 pregnancies each. Using a mean +3 SD limit, 21 of 1,414 pregnancies monitored with RIE and 21 of 1,006 monitored with RIA were interpreted as having borderline elevated values. Five of the elevated AFP values in each series represented abnormal fetuses. No neural tube defects went undetected, although one was recognized only with ultrasound. Only two of seven abnormal fetuses had a family history of neural tube defects, indicating that maternal serum AFP measurement is an important preventive measure in pregnancies that are not recognized as at high risk. The data support the use of commercially available RIA kits for amniotic fluid AFP measurement and suggest a protocol for management of elevated values.

Apert syndrome with frontonasal encephalocele.

We describe a female infant with Apert syndrome (acrocephalosyndactyly, type I) and a frontonasal encephalocele with unremarkable family history.

HeLa cell identification by analysis of ribosomal DNA segment patterns generated by endonuclease restriction.

Restriction endonuclease analysis of HeLa cells and cells in which origins have been questioned provides evidence in favor of a HeLa cell origin for the questioned cells. Digestion of cellular human DNA reveals a variable ribosomal DNA (rDNA) fragment that is present in up to four discrete sizes. Cell lines of known and suspected HeLa origin contain only two size variants. This pattern of variability serves to distinguish HeLa-derived cells from others. Despite repeated passage and divergence of the HeLa phenotype and karyotype, the restriction pattern is remarkably constant.

Molecular analysis of cloned human 18S ribosomal DNA segments.

A fraction of DNA from the human fetal lung fibroblast line IMR-90, 30-fold enriched for ribosomal DNA, was cloned in the lambda phage vector Charon 16A. Of 978 clones assayed by hybridization to a mixture of 125I-labeled 18S and 28S ribosomal RNA, 11 recombinants containing a 3.8-megadalton segment of human 18S ribosomal DNA were identified. Restriction endonuclease analysis of these clones demonstrated variation only in orientation of the human gene segment within the phage vector. Restriction sites that we had previously detected from analysis of restriction products of unfractionated human DNA by using the Southern transfer method were also present in the cloned DNA segment. Recombinant DNA technology thus provides a valid and efficient means to define structural conservation or variation within families of human genes.

Mechanism of the hypertensive effect of droperidol in pheochromocytoma.

Droperidol is used in the anaesthetic management of pheochromocytoma because of its sedative, anti-dysrhythmic and alpha-adrenoreceptor blocking properties. However, droperidol when used in pheochromocytoma, has been reported to produce a paradoxical hypertensive response. In vitro experiments with perfused rabbit ear arteries using a histochemical fluorescence technique, showed droperidol to be an inhibitor of noradrenaline uptake into sympathetic nerve endings, and this uptake inhibition was dose related. The uptake inhibition effect did not, however, produce pressor changes in experiments simulating pheochromocytoma in cats. The hypertensive response to droperidol may be due to blockade of presynaptic alpha-adrenoreceptors and this possible mechanism of action is discussed.