C329X in KRIT1 is a founder mutation among CCM patients in Sardinia

Cerebral cavernous malformations (CCMs) are CNS vascular anomalies associated with seizures, headaches and hemorrhagic strokes and represent 10–20% of cerebral lesions. CCM is present in 0.1–0.5 of the population. This disorder most often occurs sporadically but may also be familial. Familial cases are inherited as a dominant trait with incomplete penetrance and are estimated to account for KRIT1 10–40% of the patients. The identification of the genes involved in such disorders allows to characterize carriers of the mutations without clear symptoms. The first gene involved in CCM1 is KRIT1. In addition to two other genes have been described: MGC4607 (CCM2) and PDCD10 (CCM3). We selected 13 patients belonging to seven Sardinian families on the basis of clinical symptoms and Magnetic Resonance results. In MGC4607 gene an undescribed exon five deletion likely producing a truncated protein was identified in one family. In two patients with clear phenotype and in three asymptomatic relatives a 4 bp deletion in exon 9 of KRIT1 gene, leading to a premature stop codon, was detected. A unique nonsense mutation (C329X) has been found in seven patients and two asymptomatic subjects belonging to four unrelated families. Haplotype analysis revealed a common origin of this mutation. These data suggest a “founder effect” in Sardinia for the C329X mutation, similar to other mutations described in different populations.     

Monozygotic twins non-concordant for oligomeganephronic renal hypoplasia: artery-vein placental shunting as a possible pathogenetic mechanism

The etiology and pathogenesis of oligomeganephronic renal hypoplasia (OMN) are not known. In the present paper a second case of monozygotic twins non-concordant for OMN is described. It is hypothesized that one of the mechanisms which have been proposed to explain structural defects in monozygotic twins, namely placental artery-vein shunting, may have been involved in the pathogenesis of OMN in these patients. In OMN in general vascular abnormalities may have to be considered as a pathogenetic mechanism.     

A case of pneumonia following human infection with avian influenza a (H5N1)

The H5N1 infection was diagnosed in 12 patients in Turkey and confirmed by the WHO. Of these 12 patients so far, 8 have been published. In this case, we are presenting a case of pneumonia that developed following avian influenza infection in Eskisehir. Our case is one of the 4 patients who were not reported previously.     

Long-term use of cisapride (Prepulsid) in premature neonates

In order to study the effect of cisapride on gastric stasis and to evaluate the possible risk of cholestasis, 20 premature neonates born in the hospital during one year were orally treated with cisapride 0.15 mg/kg q.i.d., over a mean period of 38 days. The gestational age ranged from 26 to 34 weeks and the mean age at the start of the cisapride treatment was 18 days. All patients were ventilated, 13 had a respiratory distress syndrome (hyaline membrane disease), and 9 had gastro-oesophageal reflux (GOR). All patients were given a semielementary formula by means of a continuous nasogastric infusion. The gastric residue was studied during three days: 24 hour baseline and 48 hours under cisapride treatment. The mean residue decreased (p less than 0.0001) from 50.6% during the last 6 baseline hours to 12.1% during the last 6-hours of the cisapride period. The mean feeding volume increased from 24.2 ml to 34.2 ml (p less than 0.001). A group of four patients had reversible cholestasis against the background of an outbreak of Candida, three before and one during cisapride treatment. Therefore, it could not be demonstrated that cisapride plays a role in the development of cholestasis. Because of the risks of GOR and the drawbacks of delayed enteral feeding, it is concluded that the use of cisapride is justified in premature neonates with gastric stasis.     

Orbital Cellulitis After Strabismus Surgery

Serious infection is uncommon after eye muscle surgery. Orbital cellulitis is a rarely reported but is potentially vision- and life-threatening complication after strabismus surgery. In this report, we describe a case of unilateral orbital cellulitis after strabismus surgery for sensory exotropia in a healthy adolescent boy.     

Accurate assignment of disease liability to genetic variants using only population data

PurposeThe growing size of public variant repositories prompted us to test the accuracy of pathogenicity prediction of DNA variants using population data alone.MethodsUnder the a priori assumption that the ratio of the prevalence of variants in healthy population vs that in affected populations form 2 distinct distributions (pathogenic and benign), we used a Bayesian method to assign probability to a variant belonging to either distribution.ResultsThe approach, termed Bayesian prevalence ratio (BayPR), accurately parsed 300 of 313 expertly curated CFTR variants: 284 of 296 pathogenic/likely pathogenic variants in 1 distribution and 16 of 17 benign/likely benign variants in another. BayPR produced an area under the receiver operating characteristic curve of 0.99 for 103 functionally confirmed missense CFTR variants, which is equal to or exceeds 10 commonly used algorithms (area under the receiver operating characteristic curve range = 0.54-0.99). Application of BayPR to expertly curated variants in 8 genes associated with 7 Mendelian conditions led to the assignment of a disease-causing probability of ≥80% to 1350 of 1374 (98.3%) pathogenic/likely pathogenic variants and of ≤20% to 22 of 23 (95.7%) benign/likely benign variants.ConclusionIrrespective of the variant type or functional effect, the BayPR approach provides probabilities of pathogenicity for DNA variants responsible for Mendelian disorders using only the variant counts in affected and unaffected population samples.     

Role of transvaginal sonography in the diagnosis of peritoneal inclusion cysts.

OBJECTIVE: The aim of this prospective study was to investigate the accuracy of B-mode transvaginal sonography alone and combined with color Doppler imaging and cancer antigen 125 (CA 125) plasma concentrations in differentiating peritoneal cysts from other adnexal masses. METHODS: Between September 1999 and September 2003, 213 adnexal masses underwent transvaginal sonography combined with power Doppler evaluation. Plasma concentrations of CA 125 were measured before surgery. The sonographic suspicion of peritoneal cysts (the presence of a bizarre lump-shaped cyst with a thin wall and fine internal septations with or without an ovary suspended among adhesions) was then compared with the surgical diagnosis. The overall agreement between the sonographic test results and the surgical findings was calculated by the kappa index. The diagnostic value of each test was also evaluated with likelihood ratios (LRs). RESULTS: Thirteen of 213 patients were found to have peritoneal cysts. Specificity and sensitivity of B-mode sonography for differentiating peritoneal cysts from other adnexal masses were 96% (95% confidence interval, 94%-97%) and 62% (95% confidence interval, 35%-83%), respectively. The value of the negative LR (0.40) indicated a good clinical test, whereas the positive LR (15) indicated an excellent test. Power Doppler imaging did not seem to increase the accuracy of B-mode transvaginal sonography (kappa = 0.51 and 0.52, respectively), nor did the association of CA 125 plasma concentration (kappa = 0.34). CONCLUSIONS: Transvaginal sonography alone is a useful method for detection of peritoneal cysts.