Rett syndrome from quintuple and triple deletions within the MECP2 deletion hotspot region

Rett syndrome results from mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene, which are nearly always lethal in males and lead to regression and reduced life expectancy in females. Herein we report one propositus with five tandem deletions and a second propositus with three tandem deletions within MECP2 exon 4 that encode truncated protein products resulting in classic Rett syndrome. These deletion breakpoints and single deletions in 3 other patients were all found within a 185-bp region along with 64 of 69 other reported deletion breakpoints in the MECP2 gene. Illegitimate recombination resulting in deletion at a substantial proportion of the shared MECP2 sites is enhanced by repeated guanosine (G) DNA sequences in the antisense direction, consistent with reports at other gene loci that polypurine (multiple guanosine or adenosine (A)) basepairs enhance sequence deletion. Multiple deletions at the same poly G recombination sites confirm the existence of deletion hotspots in this gene region with numerous repeated antisense sites that are enriched 26- to 161-fold. Deletion by illegitimate recombination within a single allele can occur during mitotic or meiotic cell cycles. Although prone to disease-causing deletion, this region is unique in humans and highly conserved among mammals for the last 75 000 000 years to maintain the MECP2 gene's critical function.     

Local and distant recurrences in rectal cancer patients are predicted by the nonspecific immune response; specific immune response has only a systemic effect - a histopathological and immunohistochemical study

Background  

Invasion and metastasis is a complex process governed by the interaction of genetically altered tumor cells and the immunological and inflammatory host reponse. Specific T-cells directed against tumor cells and the nonspecific inflammatory reaction due to tissue damage, cooperate against invasive tumor cells in order to prevent recurrences. Data concerning involvement of individual cell types are readily available but little is known about the coordinate interactions between both forms of immune response.     

Pulmonary flow profile and distensibility following acute pulmonary embolism

Objective

Proof of concept study evaluating CMR as screening tool for chronic thromboembolic pulmonary hypertension (CTEPH) in patients treated for acute pulmonary embolism (PE).

Materials and methods

Right and left ventricular function of 15 consecutive patients treated for PE and 10 consecutive patients in whom PE was excluded was estimated at baseline by cardiac CT and at 6 months follow-up by CMR. Additionally, during the follow-up visit, pulmonary artery (PA) hemodynamics were studied by CMR and the presence of pulmonary hypertension by echocardiography.

Results

CT measured right ventricular ejection fraction (RVEF) was lower in patients with PE compared to patients without PE at time of diagnosis (median 47%, interquartile range 39-53 vs. 55%, 52-58; p = 0.014). After 6 months follow up, the RVEF between patients treated for PE and patients without PE were not statistically significant different (55%, 52-60 versus 54%, 51-57; p = 0.57), as were distensibility index (0.18 ± 0.18 versus 0.25 ± 0.18, p = 0.20), mean velocity (14.1 ± 3.9 cm/s versus 14.0 ± 2.5 cm/s, p = 0.81), peak velocity (86.5 ± 22 cm/s versus 89.6 ± 13 cm/s, p = 0.43) and time to peak PA blood flow velocity (142 ± 49 ms versus 161 ± 29 ms, p = 0.14). One patient was diagnosed with CTEPH and CMR revealed poor right systolic function, decreased PA distensibility and flow velocity, and a systolic notch in the PA flow profile consistent with persistent PA obstruction.

Conclusion

In this small series, right ventricular performance and PA flow profiles of patients treated for 6 months after PE are equivalent to those parameters in normal patients.     

Evaluation of laboratory assays for screening antibody to hepatitis C virus

An evaluation study, involving 11 screening methods for the detection of antibody to hepatitis C virus (anti-HCV) and a panel of 500 serum samples, was performed. Samples were tested by all 11 methods, and those showing reactivity in at least one method were studied by a combination of supplemental assays (recombinant immunoblot assays, first and second generation; neutralization test for anti-c100; synthetic peptide immunoblot assay; recombinant multi-dot immunoassay) and classified as positive (110 samples), indeterminate (4 samples), or negative (386 samples) on the basis of the results obtained. Second- generation recombinant methods performed better on positive samples than first-generation assays or synthetic peptide-based methods (99.1- 100% correlation vs. 64.5-85.5% and 93.6-99.1%, respectively), whereas the latter showed higher correlations on negative samples than recombinant assays (97.4-99.7% vs. 82.4-93%). Further investigations, using broad panels of indeterminate samples from blood donors, should be done, however, before synthetic peptide-based methods are recommended for blood bank screening. Reactivity of samples must be confirmed by one supplemental test in all cases before the donor is informed. In some cases, it may require the use of two or more different tests to obtain definite conclusions.     

Normal and disrupted lumbar longitudinal ligaments: correlative MR and anatomic study

The posterior and anterior longitudinal ligaments of the lumbar spine appear on magnetic resonance (MR) images as thin lines of very low signal intensity in all spin-echo sequences. They cover the periphery of the outer fibers of the anulus fibrosus on sagittal images. The lumbar spine of 17 patients with 19 disk herniations was prospectively evaluated with MR imaging, and these findings were correlated with surgical findings. At surgery the posterior ligament was found to be disrupted in eight cases and intact in 11. Absence of a low-signal peripheral line around the herniated nucleus pulposus (HNP) was the most reliable sign of ligament rupture (no false-negative or false-positive findings). The peripheral line appeared to be interrupted in four cases, two of which were falsely positive. The two false-positive cases were related to a chemical shift artifact between epidural fat and the HNP. Presence of a normal and continuous peripheral line outlining the HNP excluded ligament disruption. The overall sensitivity for detecting disruption was 100%, and the specificity was 78%.