Investigating 22q11.2 Deletion and Other Chromosomal Aberrations in Fetuses With Heart Defects Detected by Prenatal Echocardiography

Congenital heart disease (CHD) is the most common birth defect and the leading cause of mortality in the first year of life. In fetuses with a heart defect, chromosomal abnormalities are very frequent. Besides aneuploidy, 22q11.2 deletion is one of the most recognizable chromosomal abnormalities causing CHD. The frequency of this abnormality varies in nonselected populations. This study aimed to investigate the incidence of the 22q11.2 deletion and other chromosomal alterations in a Brazilian sample of fetuses with structural cardiac anomalies detected by fetal echocardiography. In a prospective study, 68 fetuses with a heart defect were evaluated. Prenatal detection of cardiac abnormalities led to identification of aneuploidy or structural chromosomal anomaly in 35.3% of these cases. None of the fetuses with apparently normal karyotypes had a 22q11.2 deletion. The heart defects most frequently associated with chromosomal abnormalities were atrioventricular septal defect (AVSD), ventricular septal defect (VSD), and tetralogy of Fallot. Autosomal trisomies 18 and 21 were the most common chromosomal abnormalities. The study results support the strong association of chromosome alterations and cardiac malformation, especially in AVSD and VSD, for which a chromosome investigation is indicated. In fetuses with an isolated conotruncal cardiopathy, fluorescence in situ hybridization (FISH) to investigate a 22q11.2 deletion is not indicated.

Decreased AIRE Expression and Global Thymic Hypofunction in Down Syndrome

The Down syndrome (DS) immune phenotype is characterized by thymus hypotrophy, higher propensity to organ-specific autoimmune disorders, and higher susceptibility to infections, among other features. Considering that AIRE (autoimmune regulator) is located on 21q22.3, we analyzed protein and gene expression in surgically removed thymuses from 14 DS patients with congenital heart defects, who were compared with 42 age-matched controls with heart anomaly as an isolated malformation. Immunohistochemistry revealed 70.48 +/- 49.59 AIRE-positive cells/mm(2) in DS versus 154.70 +/- 61.16 AIRE-positive cells/mm(2) in controls (p < 0.0001), and quantitative PCR as well as DNA microarray data confirmed those results. The number of FOXP3-positive cells/mm(2) was equivalent in both groups. Thymus transcriptome analysis showed 407 genes significantly hypoexpressed in DS, most of which were related, according to network transcriptional analysis (FunNet), to cell division and to immunity. Immune response-related genes included those involved in 1) Ag processing and presentation (HLA-DQB1, HLA-DRB3, CD1A, CD1B, CD1C, ERAP) and 2) thymic T cell differentiation (IL2RG, RAG2, CD3D, CD3E, PRDX2, CDK6) and selection (SH2D1A, CD74). It is noteworthy that relevant AIRE-partner genes, such as TOP2A, LAMNB1, and NUP93, were found hypoexpressed in DNA microarrays and quantitative real-time PCR analyses. These findings on global thymic hypofunction in DS revealed molecular mechanisms underlying DS immune phenotype and strongly suggest that DS immune abnormalities are present since early development, rather than being a consequence of precocious aging, as widely hypothesized. Thus, DS should be considered as a non-monogenic primary immunodeficiency. The Journal of Immunology, 2011, 187: 3422-3430.

De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot

Tetralogy of Fallot (TOF), the most common severe congenital heart malformation, occurs sporadically, without other anomaly, and from unknown cause in 70% of cases. Through a genome-wide survey of 114 subjects with TOF and their unaffected parents, we identified 11 de novo copy number variants (CNVs) that were absent or extremely rare (<0.1%) in 2,265 controls. We then examined a second, independent TOF cohort (n = 398) for additional CNVs at these loci. We identified CNVs at chromosome 1q21.1 in 1% (5/512, P = 0.0002, OR = 22.3) of nonsyndromic sporadic TOF cases. We also identified recurrent CNVs at 3p25.1, 7p21.3 and 22q11.2. CNVs in a single subject with TOF occurred at six loci, two that encode known (NOTCH1, JAG1) disease-associated genes. Our findings predict that at least 10% (4.5-15.5%, 95% confidence interval) of sporadic nonsyndromic TOF cases result from de novo CNVs and suggest that mutations within these loci might be etiologic in other cases of TOF.

Absence of bifurcation of the portal vein

Absence of the horizontal segment of the left portal vein (PV) or absence of bifurcation of the portal vein (ABPV) is extremely rare anomaly. The aim of this study was to study the extra-hepatic PV demonstrating the importance of its careful assessment for the purpose of split-liver transplantation. Human cadaver livers (n = 60) were obtained from routine autopsies. The cutting plane of the liver consisted of a longitudinal section made immediately on the left of the supra-hepatic inferior vena cava through the gallbladder bed preserving the arterial, portal and biliary branches in order to obtain two viable grafts (right lobe-segments V, VI, VII, and VIII and left lobe-segments II, III, and IV) as defined by the main portal scissure. The PV was dissected out and recorded for application of the liver splitting. The PV trunk has been divided into right and left branch in 50 (83.3%) cases. A trifurcation of the PV was found in 9 (15.2%) cases, 3 (5%) was a right anterior segmental PV arising from the left PV and 6 (10%) a right posterior segmental PV arising from the main PV. ABPV occurred in 1 (1.6%) case. Absence of bifurcation of the portal vein is a rare anatomic variation, the surgeon must be cautious and aware of the existence of this exceptional PV anomaly either pre or intra-operatively for the purpose of hepatectomies or even split-liver transplantation.

Ophthalmic Considerations in the Management of Tessier Cleft 5/9

Purpose: To describe a patient with Tessier cleft number 5 and 9 and review the literature on the ocular impairment and management of this extremely rare anomaly. Methods: Interventional case report and literature review. Results: The literature review showed that the present patient is the second case with clefts 5/9. The ophthalmic consequences of this rare association are virtually unreported. Our case demonstrates that the presence of cleft number 9 adds a cicatricial component on the upper eyelid that severely impairs the dynamics of this lid. The corneal status of the patient was successfully managed with simultaneous upper eyelid lengthening and facial reconstruction. Conclusion: In order to avoid corneal perforation, simultaneous upper and lower eyelid reconstruction is mandatory in cases of cleft 5/9. The affected patients should be continuously followed in order to prevent amblyopia.

Progressive bilateral enophthalmos associated with cerebrospinal shunting

A 22-year-old woman was examined for a complaint of bilateral progressive enophthalmos that had begun after the cerebrospinal fluid shunting procedure 9 years ago. Photographs and CT scans taken before surgery proved that the position of her eyes was normal before surgery. The enophthalmos was so severe that it induced a poor eyelid-globe apposition with trichiasis and superficial keratopathy. CT of the orbits showed that both orbital roofs were arched and displaced toward the anterior cranial fossa. The placement of porous polyethylene sheets on the orbital roofs through a coronal approach corrected the eye position. A literature review indicated that cerebrospinal shuntings are plagued by a variety of complications including bone changes and craniosynostosis. We believe that enophthalmos associated with cerebrospinal fluid shunting results from a rare acquired bony orbital anomaly.

Dielectric properties and physical features of phosphate glasses containing iron oxide

Microwave techniques were applied to the study of dielectric properties of phosphate glasses on the basis of contributions from permanent and induced dipolar polarization of local structural units interacting with the electrical component of the electromagnetic radiation. The dielectric constant of the selected glass system (100-x)(50P(2)O(5)center dot 25Li(2)O center dot 25Na(2)O)center dot xFe(2)O(3), where 0 <= x <= 21 is in mol%, was measured using a microwave setup assembled to measure the phase shift of the standing wave pattern produced by the insertion of the sample. It is shown that the Fe2+ ions contribute effectively to the dielectric constant, as expected from the interactions of the dipoles of the local charge compensation pairs with the microwave radiation. However, there is the possibility of occurrence of some ions Fe3+, in general, at low iron content, which reinforces the glass structure and, therefore, decreases the dielectric constant. There is a gradual conversion from Fe3+ to Fe2+ as the iron ions increases. This is possibly the reason of the anomaly in the dielectric constant values observed in the results. These assumptions can be checked by results of electronic paramagnetic resonance (EPR) and optical absorption (OA). The dielectric constant of the glasses studied in this work was found to increase with the temperature in the range of 25-330 degrees C. (C) 2007 Elsevier B.V. All rights reserved.

Right coronary artery fistula to the coronary sinus and right atrium associated with giant right coronary enlargement detected by transthoracic echocardiography

We present the case of a 54-year-old female with a previous history of lung fibrosis secondary to methotrexate used for rheumatoid arthritis who was referred to cardiology evaluation due to precordial pain. Echocardiography showed biatrial enlargement with an enlarged coronary sinus and tubular image posterior to the heart. On the coronary angiogram, the right coronary artery was enlarged, and a distal fistula was identified. The patient underwent a contrast enhanced cardiac computed tomography which demonstrated an aneurysmatic right coronary artery with a distal fistula to the right atrium and coronary sinus. As the chest pain did not recur and there was a high risk of the intervention to correct coronary fistula, the patient remained on conservative treatment.

Summertime moisture transport over Southeastern South America and extratropical cyclones behavior during inter-El Nio events

The impact of the inter-El Nio (EN) variability on the moisture availability over Southeastern South America (SESA) is investigated. Also, an automatic tracking scheme was used to analyze the extratropical cyclones properties (system density - SD and central pressure - CP) in this region. During the austral summer period from 1977-2000, the differences for the upper-level wave train anomaly composites seem to determine the rainfall composite differences. In fact, the positive rainfall anomalies over most of the SESA domain during the strong EN events are explained by an upper-level cyclonic center over the tropics and an anticyclonic center over the eastern subtropical area. This pattern seems to contribute to upward vertical motion at 500 hPa and reinforcement of the meridional moisture transport from the equatorial Atlantic Ocean and western Amazon basin to the SESA region. These features may contribute to the positive SD and negative CP anomalies explaining part of the positive rainfall anomalies found there. On the other hand, negative rainfall anomalies are located in the northern part of SESA for the weak EN years when compared to those for the strong events. Also, positive anomalies are found in the southern part, albeit less intense. It was associated with the weakening of the meridional moisture transport from the tropics to the SESA that seems have to contributed with smaller SD and CP anomalies over the most part of subtropics, when compared to the strong EN years.

An event of stratospheric air intrusion and its associated secondary surface cyclogenesis over the South Atlantic Ocean

This work presents an analysis of a lowermost stratospheric air intrusion event over the coast of Brazil, which may have been responsible for a secondary surface cyclogenesis over the southwestern Atlantic Ocean. The surface cyclone initiated at 0600 UTC 17 April 1999 in a cold air mass in the rear of a cold front after a primary cyclone developed over the same region. The analysis of the secondary cyclone revealed the presence of lowermost stratospheric air intrusion characterized by anomalous potential vorticity (PV), dry air, and high concentration of ozone in atmospheric column. The system developed on the eastern side of an upper level core of PV anomaly, which induced a cyclonic wind circulation at lower levels and favored the onset of the secondary cyclone. In midlevels (500 hPa), the cutoff low development contributed to reduce the propagation speed of the wave pattern. This feature seemed to (1) allow the low-level cold/dry air to heat/moisten associated with sensible and latent fluxes transferred from the ocean to the atmosphere, which intensified a baroclinic zone parallel to the coast, and (2) contribute to the long duration of the system. The present analysis indicates that this secondary cyclone development could be the result of the coupling between the PV anomaly in the upper levels and low-level air-sea interaction.

Intraseasonal and Interannual Variability of Extreme Dry and Wet Events over Southeastern South America and the Subtropical Atlantic during Austral Summer

Intraseasonal and interannual variability of extreme wet and dry anomalies over southeastern Brazil and the western subtropical South Atlantic Ocean are investigated. Precipitation data are obtained from the Global Precipitation Climatology Project (GPCP) in pentads during 23 austral summers (December-February 1979/80-2001/02). Extreme wet (dry) events are defined according to 75th (25th) percentiles of precipitation anomaly distributions observed in two time scales: intraseasonal and interannual. The agreement between the 25th and 75th percentiles of the GPCP precipitation and gridded precipitation obtained from stations in Brazil is also examined. Variations of extreme wet and dry anomalies on interannual time scales are investigated along with variations of sea surface temperature (SST) and circulation anomalies. The South Atlantic SST dipole seems related to interannual variations of extreme precipitation events over southeastern Brazil. It is shown that extreme wet and dry events in the continental portion of the South Atlantic convergence zone (SACZ) are decoupled from extremes over the oceanic portion of the SACZ and there is no coherent dipole of extreme precipitation regimes between tropics and subtropics on interannual time scales. On intraseasonal time scales, the occurrence of extreme dry and wet events depends on the propagation phase of extratropical wave trains and consequent intensification (weakening) of 200-hPa zonal winds. Extreme wet and dry events over southeastern Brazil and subtropical Atlantic are in phase on intraseasonal time scales. Extreme wet events over southeastern Brazil and subtropical Atlantic are observed in association with low-level northerly winds above the 75th percentile of the seasonal climatology over central-eastern South America. Extreme wet events on intraseasonal time scales over southeastern Brazil are more frequent during seasons not classified as extreme wet or dry on interannual time scales.

Upper-mantle seismic structure beneath SE and Central Brazil from P- and S-wave regional traveltime tomography

We present models for the upper-mantle velocity structure beneath SE and Central Brazil using independent tomographic inversions of P- and S-wave relative arrival-time residuals (including core phases) from teleseismic earthquakes. The events were recorded by a total of 92 stations deployed through different projects, institutions and time periods during the years 1992-2004. Our results show correlations with the main tectonic structures and reveal new anomalies not yet observed in previous works. All interpretations are based on robust anomalies, which appear in the different inversions for P-and S-waves. The resolution is variable through our study volume and has been analyzed through different theoretical test inversions. High-velocity anomalies are observed in the western portion of the Sao Francisco Craton, supporting the hypothesis that this Craton was part of a major Neoproterozoic plate (San Franciscan Plate). Low-velocity anomalies beneath the Tocantins Province (mainly fold belts between the Amazon and Sao Francisco Cratons) are interpreted as due to lithospheric thinning, which is consistent with the good correlation between intraplate seismicity and low-velocity anomalies in this region. Our results show that the basement of the Parana Basin is formed by several blocks, separated by suture zones, according to model of Milani & Ramos. The slab of the Nazca Plate can be observed as a high-velocity anomaly beneath the Parana Basin, between the depths of 700 and 1200 km. Further, we confirm the low-velocity anomaly in the NE area of the Parana Basin which has been interpreted by VanDecar et al. as a fossil conduct of the Tristan da Cunha Plume related to the Parana flood basalt eruptions during the opening of the South Atlantic.

Integrated marine gravity field in the Brazilian coast from altimeter-derived sea surface gradient and shipborne gravity

Sea surface gradients derived from the Geosat and ERS-1 satellite altimetry geodetic missions were integrated with marine gravity data from the National Geophysical Data Center and Brazilian national surveys. Using the least squares collocation method, models of free-air gravity anomaly and geoid height were calculated for the coast of Brazil with a resolution of 2` x 2`. The integration of satellite and shipborne data showed better statistical results in regions near the coast than using satellite data only, suggesting an improvement when compared to the state-of-the-art global gravity models. Furthermore, these results were obtained with considerably less input information than was used by those reference models. The least squares collocation presented a very low content of high-frequency noise in the predicted gravity anomalies. This may be considered essential to improve the high resolution representation of the gravity field in regions of ocean-continent transition. (C) 2010 Elsevier Ltd. All rights reserved.

Magnetotelluric deep soundings, gravity and geoid in the south Sao Francisco craton: Geophysical indicators of cratonic lithosphere rejuvenation and crustal underplating

In the south Sao Francisco craton a circular and 8-m amplitude geoid anomaly coincides with the outcropping terrain of an Archean-Paleoproterozoic basement. Broadband magnetotelluric (MT) data inversions of two radial profiles within the positive geoid and Bouguer gravity anomaly yield geo-electrical crustal sections, whereby the lower crust is locally more conductive (10 to 100 Omega m) in spatial coincidence with a denser lower crust modeled by the gravity data. This anomalous lower crust may have resulted from magmatic underplating, associated with Mesoarchean and Proterozoic episodes of tholeiitic dike intrusion. Long-period MT soundings reveal a low electrical resistivity mantle (20 to 200 Omega m) from depths beyond 120 km. Forward geoid modeling, using the scope of the low electrical resistivity region within the mantle as a constraint, entails a density increase (40 to 50 kg/m(3)) possibly due to Fe enrichment of mantle minerals. However, this factor alone does not explain the observed resistivity. A supplemented presence of small amounts of percolated carbonatite melting (similar to 0.005 vol.%), dissolved water and enhanced oxygen fugacity within the peridotitic mantle are viable agents that could explain the less resistive upper mantle. We propose that metasomatic processes confined in the sub-continental lithospheric mantle foster the conditions for a low degree melting with variable CO(2), H(2)O and Fe content. Even though the precise age of this metasomatism is unknown it might be older than the Early Cretaceous based on the evidence that a high-degree of melting in a lithospheric mantle impregnated with carbonatites originated the tholeiitic dike intrusions dispersed from the southeastern border of the Sao Francisco craton, during the onset of the lithosphere extension and break-up of the western Gondwana. The proxies are the NE Parana and Espinhaco (130 Ma, Ar/Ar ages) tholeiitic dikes, which contain (similar to 3%) carbonatites in their composition. The occurrence of a positive geoid anomaly (+ 10 m) and pre-tholeiites (age > 138 Ma), carbonatites and kimberlites along the west African continental margin (Angola and Namibia) reinforces the presumed age of the Sao Francisco-Congo craton rejuvenation to be prior to its fragmentation in the Lower Cretaceous. (C) 2010 Elsevier B.V. All rights reserved.

Reappraisal of the effective elastic thickness for the sub-Andes using 3-D finite element flexural modelling, gravity and geological constraints

P>Estimates of effective elastic thickness (T(e)) for the western portion of the South American Plate using, independently, forward flexural modelling and coherence analysis, suggest different thermomechanical properties for the same continental lithosphere. We present a review of these T(e) estimates and carry out a critical reappraisal using a common methodology of 3-D finite element method to solve a differential equation for the bending of a thin elastic plate. The finite element flexural model incorporates lateral variations of T(e) and the Andes topography as the load. Three T(e) maps for the entire Andes were analysed: Stewart & Watts (1997), Tassara et al. (2007) and Perez-Gussinye et al. (2007). The predicted flexural deformation obtained for each T(e) map was compared with the depth to the base of the foreland basin sequence. Likewise, the gravity effect of flexurally induced crust-mantle deformation was compared with the observed Bouguer gravity. T(e) estimates using forward flexural modelling by Stewart & Watts (1997) better predict the geological and gravity data for most of the Andean system, particularly in the Central Andes, where T(e) ranges from greater than 70 km in the sub-Andes to less than 15 km under the Andes Cordillera. The misfit between the calculated and observed foreland basin subsidence and the gravity anomaly for the Maranon basin in Peru and the Bermejo basin in Argentina, regardless of the assumed T(e) map, may be due to a dynamic topography component associated with the shallow subduction of the Nazca Plate beneath the Andes at these latitudes.