Phenotypic diversity in patients with multiple serrated polyps: a genetics clinic study.

OBJECTIVE: Hyperplastic polyposis is a colonic polyposis condition of unknown aetiology. The purpose of this study was to examine the spectrum of phenotypic variation in patients with multiple serrated polyps as a basis for gene discovery. METHODS: One hundred and twenty-six patients with multiple (> or = 5) serrated polyps were recruited to the study. Polyp counts were extracted from histology and colonoscopy reports. Ethnicity was self-reported. Family history of cancer data were derived from pedigrees. Ascertainment status was classified as either index case or identified by screening. RESULTS: The average reported polyp count was 39. Patients with highest polyp numbers were more likely to be male (P = 0.02). Colorectal cancer (CRC) was identified in 49 of 119 patients (41%) and 28% of these patients had multiple CRC. Young onset patients had higher polyp numbers (P = 0.03) and were more likely to have their CRC in the distal colon (P = 0.02). CRC was significantly associated with the presence of adenomas (P = 0.03). Patients were divided into moderate polyposis (5-79 serrated polyps) and dense polyposis (80 or more) categories. The dense polyposis category was associated with a lack of family history for CRC (P = 0.034) and male gender (P = 0.014), independent of ascertainment status and recruitment site. CONCLUSION: Multiple serrated polyps were associated with an increased personal risk of CRC. A subset of patients with the highest polyp numbers was more likely to be male and to have no family history of CRC. This result suggests heterogeneous modes of inheritance and has implications for studies investigating the genetic basis of multiple serrated polyps.

The geneticist's role in adult congenital heart disease.

The Human Genome Project promises to revolutionize our understanding and approach to human diseases. It promises to identify the genes and pathways involved in normal cardiac development and to determine the impact of mutations in these genes in the pathogenesis of syndromic and nonsyndromic congenital heart defects. Some of these advances in genetic knowledge are being translated into clinical care, raising the question of what role this knowledge should have in the adult congenital heart disease (ACHD) clinic. The authors summarize the clinical and molecular advances relevant to the care and genetic counseling of ACHD patients and explore the role of genetic care providers in an ACHD clinic.

Perinatal antibiotic usage and changes in colonization and resistance rates of group B streptococcus and other pathogens.

OBJECTIVE: To quantify current antibiotic usage during the perinatal period and impact on vaginal-rectal colonizing organism resistance rates. METHODS: Swabs were obtained for culture of group B streptococcus and other bacteria from a cohort of 1207 pregnant women in Calgary, Alberta, at 36 weeks' gestation. Those women who received antibiotics during labor or after pregnancy and a 10% subset who received no antibiotics had repeat cultures at 6 weeks postpartum. Cultured organisms were tested for sensitivity to several antibiotics. RESULTS: Group B streptococcus was identified in 235 women (19.5%) in the antepartum period. Fifty-one percent of all participants received antibiotics (31.4% intrapartum). Group B streptococcus prophylaxis was given to 215 (17.8%), whereas 83 (6.9%) group B streptococcus-negative women without fever during labor received antibiotics. Ampicillin (49%), cefazolin (28%), and penicillin (18%) were the most frequently used antibiotics. Resistance rates among group B streptococcus to erythromycin and clindamycin were 5.6% and 3.0%, respectively, whereas 20.6% of Escherichia coli were ampicillin resistant. Among antibiotic recipients, 6.3% of all bacteria that were initially sensitive on prenatal cultures to a specific antibiotic became resistant in the postnatal period, whereas 6.5% that were initially resistant became sensitive. CONCLUSION: Current prevention practices in our region were associated with perinatal antibiotic administration in over half of pregnant women. Ampicillin was the most common antibiotic administered. Some physicians are treating women who are group B streptococcus culture negative at term, a practice that is of no proven value. However, this was not associated with increased resistance for group B streptococcus or other organisms identified from maternal vaginal-rectal tracts.

Congenital muscle fiber-type disproportion in a patient with congenital central hypoventilation syndrome due to PHOX2B mutations.

Increasing numbers of genetic origins are being reported for congenital muscle fiber-type disproportion. Most of these identified disorders are genetic myopathies. This is the first case report (to our knowledge) demonstrating congenital central hypoventilation syndrome due to PHOX2B mutations with congenital muscle fiber-type disproportion. The muscle histopathologic findings in the patient showed no changes of disuse atrophy and suggest that PHOX2B mutations may have an additional role in muscle development, contributing to respiratory failure in congenital central hypoventilation syndrome.

Supravalvar aortic stenosis with supravalvar pulmonary stenosis and peripheral vascular stenoses.

A non-dysmorphic 10 month old female was discovered at surgery to have severe vasculopathy of both the systemic and pulmonary arteries. These findings were confirmed by pathologic examination. Follow-up angiography has confirmed multiple sites of vascular obstruction which appear to be worsening. Angioplasty has only partially relieved these obstructions. The pathology and possible etiology are reviewed.

Trafficking of L-type calcium channels mediated by the postsynaptic scaffolding protein AKAP79.

Accurate calcium signaling requires spatial and temporal coordination of voltage-gated calcium channels (VGCCs) and a variety of signal transduction proteins. Accordingly, regulation of L-type VGCCs involves the assembly of complexes that include the channel subunits, protein kinase A (PKA), protein kinase A anchoring proteins (AKAPs), and beta2-adrenergic receptors, although the molecular details underlying these interactions remain enigmatic. We show here, by combining extracellular epitope splicing into the channel pore-forming subunit and immunoassays with whole cell and single channel electrophysiological recordings, that AKAP79 directly regulates cell surface expression of L-type calcium channels independently of PKA. This regulation involves a short polyproline sequence contained specifically within the II-III cytoplasmic loop of the channel. Thus we propose a novel mechanism whereby AKAP79 and L-type VGCCs function as components of a biosynthetic mechanism that favors membrane incorporation of organized molecular complexes in a manner that is independent of PKA phosphorylation events.