Autism spectrum disorder recurrence, resulting of germline mosaicism for a CHD2 gene missense variant.

Germline mosaicism for a novel missense variant p.Thr645Met located in the SNF2-related ATP dependent helicase domain of CHD2 in 2 affected siblings with autism spectrum disorder.

Search for ReCQL4 mutations in 39 patients genotyped for suspected Rothmund-Thomson/Baller-Gerold syndromes.

Three overlapping conditions, namely Rothmund-Thomson (RTS), Baller-Gerold (BGS) and RAPADILINO syndromes, have been attributed to RECQL4 mutations. Differential diagnoses depend on the clinical presentation, but the numbers of known genes remain low, leading to the widespread prescription of RECQL4 sequencing. The aim of our study was therefore to determine the best clinical indicators for the presence of RECQL4 mutations in a series of 39 patients referred for RECQL4 molecular analysis and belonging to the RTS (27 cases) and BGS (12 cases) spectrum. One or two deleterious RECQL4 mutations were found in 10/27 patients referred for RTS diagnosis. Clinical and molecular reevaluation led to a different diagnosis in 7/17 negative cases, including Clericuzio-type poikiloderma with neutropenia, hereditary sclerosing poikiloderma, and craniosynostosis/anal anomalies/porokeratosis. No RECQL4 mutations were found in the BGS group without poikiloderma, confirming that RECQL4 sequencing was not indicated in this phenotype. One chromosomal abnormality and one TWIST mutation was found in this cohort. This study highlights the search for differential diagnoses before the prescription of RECQL4 sequencing in this clinically heterogeneous group. The combination of clinically defined subgroups and next-generation sequencing will hopefully bring to light new molecular bases of syndromes with poikiloderma, as well as BGS without poikiloderma.

Balanced complex chromosome rearrangement in male infertility: case report and literature review.

Complex chromosome rearrangements (CCRs) are structural rearrangements involving at least three chromosomes and three or more chromosome breakpoints. Generally, balanced CCR carriers have a normal phenotype but they are at a higher reproductive risk. Azoospermia was discovered in the male partner of a couple with primary infertility. Conventional cytogenetics identified a CCR refined by fluorescent in situ hybridisation. The CCR involved three chromosomes, four breakpoints and an insertion. A literature search identified 43 phenotypically normal males referred for reproductive problems presenting a CCR. More males were ascertained because of spermatogenesis failure or disturbances than because of repeated abortions and/or birth of a malformed child. Male carriers of CCR produce a high frequency of chromosomally abnormal spermatozoa due to the aberrant segregation of the rearranged chromosomes. The number of chromosomes and breakpoints involved in the rearrangement, the position of breakpoints, the relative size of the resultant chromosomes and the presence or absence of recombination inside the paired-rearranged segments are presumed to affect the fertility of the carrier. Testicular biopsy should not be performed in males with azoospermia. Intracytoplasmic sperm injection should not be proposed as a procedure for treating the infertility of CCR male carriers as a successful result is unlikely.

A gene for Holt-Oram syndrome maps to the distal long arm of chromosome 12.

Holt-Oram syndrome (HOS) is an autosomal dominant condition of unknown origin characterized by congenital septal heart defects with associated malformations of the upper limbs (radial ray). Here, we report on the mapping of a gene causing HOS to the distal long arm of chromosome 12 (12q21-qter) by linkage analysis in nine informative families (Zmax = 6.81 at theta = 0 at the D12S354 locus). Also, multipoint linkage analysis places the HOS gene within the genetic interval between D12S84 and D12S79 (multipoint lod-score in log base 10 = 8.10). The mapping of a gene for HOS is, to our knowledge, the first chromosomal localization of a gene responsible for congenital septal heart defect in human. The characterization of the HOS gene will hopefully shed light on the molecular mechanisms that govern heart septation in the early stages of embryogenesis.

Efficient surface formation route of interstellar hydroxylamine through NO hydrogenation. I. The submonolayer regime on interstellar relevant substrates.

Dust grains in the interstellar medium are known to serve as the first chemical laboratory where the rich inventory of interstellar molecules are synthesized. Here we present a study of the formation of hydroxylamine--NH(2)OH--via the non-energetic route NO + H (D) on crystalline H(2)O and amorphous silicate under conditions relevant to interstellar dense clouds. Formation of nitrous oxide (N(2)O) and water (H(2)O, D(2)O) is also observed and the reaction network is discussed. Hydroxylamine and water results are detected in temperature-programmed desorption (TPD) experiments, while N(2)O is detected by both reflection-absorption IR spectroscopy and TPD techniques. The solid state NO + H reaction channel proves to be a very efficient pathway to NH(2)OH formation in space and may be a potential starting point for prebiotic species in dark interstellar clouds. The present findings are an important step forward in understanding the inclusion of interstellar nitrogen into a non-volatile aminated species since NH(2)OH provides a solid state nitrogen reservoir along the whole evolutionary process of interstellar ices from dark clouds to planetary systems.

KI and TEDA influences towards the retention of radiotoxic CH3I by activated carbons.

Activated carbons (AC) are widely used within the ventilation networks of nuclear facilities to trap volatile iodine species. In this paper, the performances of various commercial activated carbons towards the trapping of γ-labelled methyl iodide were evaluated in semi-pilot scale under different R.H. according to normalized procedures. A combination between the retention performances and the physico-chemical properties as deduced from several techniques was performed to gain insights about the AC influencing parameters on γ-CH3I capture. Different trends were obtained depending on the impregnant nature and the studied conditions. A high sensitivity of KI/AC towards water vapor was outlined. At R.H. = 40%. The enhancement of water uptake by KI/AC as deduced from water adsorption experiments, leads to decrease the available microporosity for CH3I physisorption, inducing therefore the reduction of performances as a function of KI content at these conditions. At R.H. = 90%, the adsorption mechanism was found to be governed by isotopic exchange reaction since 90% of the microporosity was occupied by water molecules. Therefore, a slight increase of DF was obtained in these conditions. This sensitivity was found to be of a lesser extent for TEDA/AC displaying the highest retention performances whatever the studied condition.

Are IVC filters required in combat support hospitals?

BACKGROUND: Haemorrhagic shock from traumatic injuries is now often treated using a damage control resuscitation strategy that transfuses packed red blood cells, plasma and platelets in a 1:1:1 ratio, early use of activated recombinant factor VII and transfusion of fresh whole blood. These therapies are aimed at promoting thrombosis in injured vessels. Such patients are at high risk for thrombotic complications and thromboprophylaxis is necessary, but frequently impossible to use in the early phase of care. CASE PRESENTATION: We describe the case of an Afghan civilian worker who suffered a vertical shear pelvic fracture with massive bleeding in a pedestrian/truck collision that was treated with a damage control resuscitation strategy, and who later suffered a severe pulmonary embolus. The potential use of a temporary inferior vena cava [IVC] filters is discussed. RECOMMENDATIONS: Care providers and policy makers must recognize that the increased use of prothrombotic strategies of resuscitation will likely increase the incidence of thrombotic complications in the high risk population of severely injured patients in combat support hospitals. Monitoring the incidence of these complications and development of strategies for prevention and treatment are required to avoid undermining the positive outcomes of damage control resuscitation. These strategies could include supplying combat support hospitals with the equipment and training necessary for placement of temporary IVC filters under fluoroscopic guidance.

Clinical, molecular, and genotype-phenotype correlation studies from 25 cases of oral-facial-digital syndrome type 1: a French and Belgian collaborative study.

Oral-facial-digital syndrome type 1 (OFD1) is characterised by an X linked dominant mode of inheritance with lethality in males. Clinical features include facial dysmorphism with oral, tooth, and distal abnormalities, polycystic kidney disease, and central nervous system malformations. Large interfamilial and intrafamilial clinical variability has been widely reported, and 18 distinct mutations have been previously reported within OFD1. A French and Belgian collaborative study collected 25 cases from 16 families. OFD1 was analysed using direct sequencing and phenotype-genotype correlation was performed using chi2 test. X inactivation studies were performed on blood lymphocytes. In 11 families, 11 novel mutations, including nine frameshift, one nonsense, and one missense mutation were identified, which spanned nine different exons. A combination of our results with previously reported cases showed that the majority of mutations (65.5%) was located in exons 3, 8, 9, 13, and 16. There was phenotype-genotype correlation between (a) polycystic kidney disease and splice mutations; (b) mental retardation and mutations located in exons 3, 8, 9, 13, and 16; and (c) tooth abnormalities and mutations located in coiled coil domains. Comparing the phenotype of the families with a pathogenic mutation to families with absence of OFD1 mutation, polycystic kidneys and short stature were significantly more frequent in the group with no OFD1 mutation, whereas lingual hamartomas were significantly more frequent in the group with OFD1 mutation. Finally, an X inactivation study showed non-random X inactivation in a third of the samples. Differential X inactivation between mothers and daughters in two families with high intrafamilial variability was of particular interest. Slight phenotype-genotype correlations were established, and X inactivation study showed that skewed X inactivation could be partially involved in the pathogenesis of intrafamilial clinical variability.

NEXAFS study of multi-walled carbon nanotubes functionalization with sulfonated poly(ether ether ketone) chains.

Functionalization of multi-walled carbon nanotubes (MWNTs) surface by sulfonated poly (ether ether ketone) SPEEK chains using a direct attachment reaction was investigated. A two step method was performed. MWNTs were oxidized by a nitric acid treatment to generate carboxyl groups on their surface. The grafting reaction of sulfonated groups of SPEEK with carboxyl groups present on the surface of oxidized MWNTs readily proceeds by using hexane diamine as an interlinking molecule. Transmission electron microscopy (TEM) shows that tubes are wrapped by polymer chains. Near edge X-ray absorption fine structure spectroscopy (NEXAFS) at the C K-edge, O K-edge, and N K-edge and X-ray photoelectron spectroscopy (XPS) were used to give evidence of covalent functionalization of MWNTs by SPEEK macromolecules.

Spectroscopic study of nitrogen doping of multi-walled carbon nanotubes.

Combined spatially resolved electron-energy loss spectroscopy (EELS) and high resolution near-edge X-ray absorption fine structure (NEXAFS) spectroscopy have been used to investigate the nitrogen doping of multi-walled carbon nanotubes (N-MWNT). EELS indicates that most of the tubes are nitrogen-doped. NEXAFS spectroscopy reveals pyridine-like and nitrile N structures. High resolution NEXAFS experiments show that the main nitrogen concentration originates from a high amount of molecular N2 encapsulated into only a small quantity of tubes.

Prenatal diagnosis of a mosaic 45,X/46,X,r(X)46,XX with a small ring of the X chromosome.

We report the prenatal diagnosis of a mosaic 45,X/46,X,r(X)/46,XX foetus after amniocentesis for maternal second-trimester serum screening. Biparental contribution for the X chromosomes suggest the postzygotic formation of the X ring. The ring is tiny but contains the X-inactive-specific transcript gene (XIST). However, we could not determine whether XIST was correctly expressed or not. The foetal ultrasound examination at 21, 25, 31 weeks' gestation showed no physical abnormalities, prompting the parents to continue the pregnancy. Physical examination at one year-old revealed normal growth and psychomotor development. Only three cases exhibiting an identical 45,X/46,X,r(X)/46,XX mosaicism, but detected postnatally, are reported in the literature. This is the first reported case ofa mosaic 45,X/46,X,r(X)/46,XX identified in the prenatal period.

First in-flight synchrotron X-ray absorption and photoemission study of carbon soot nanoparticles.

Many studies have been conducted on the environmental impacts of combustion generated aerosols. Due to their complex composition and morphology, their chemical reactivity is not well understood and new developments of analysis methods are needed. We report the first demonstration of in-flight X-ray based characterizations of freshly emitted soot particles, which is of paramount importance for understanding the role of one of the main anthropogenic particulate contributors to global climate change. Soot particles, produced by a burner for several air-to-fuel ratios, were injected through an aerodynamic lens, focusing them to a region where they interacted with synchrotron radiation. X-ray photoelectron spectroscopy and carbon K-edge near-edge X-ray absorption spectroscopy were performed and compared to those obtained for supported samples. A good agreement is found between these samples, although slight oxidation is observed for supported samples. Our experiments demonstrate that NEXAFS characterization of supported samples provides relevant information on soot composition, with limited effects of contamination or ageing under ambient storage conditions. The highly surface sensitive XPS experiments of airborne soot indicate that the oxidation is different at the surface as compared to the bulk probed by NEXAFS. We also report changes in soot's work function obtained at different combustion conditions.

Fetal aqueductal glioneuronal hamartoma: a clinicopathological and physiopathological study of three cases.

UNLABELLED: Fetal hydrocephalus due to aqueductal stenosis is classified into two main groups: congenital (X-linked, atresia, septa and forking) and acquired (post-infectious or post-hemorrhagic, gliosis and tumors). MATERIAL AND METHODS: We report three fetal cases presenting with severe hydrocephalus, two of which being apparently sporadic, and the third possibly inherited. On macroscopic examination, no associated malformations were identified, either craniofacial dysmorphy, or visceral abnormalities. Neuropathological study revealed massive hydrocephalus caused by narrowing of the Aqueduct of Sylvius. Histological examination evidenced a nodular, well-demarcated mass producing into the aqueductal lumen, and containing numerous immature proliferating glioneuronal cells. Immunohistochemical analyses did not suggest a developmental abnormality of the subcommissural organ but rather a hamartomatous malformative process. RESULTS: Hamartoma of the posterior fossa has been rarely reported. Post-natal cases have been described in the cerebello-pontine angle or in the quadrigeminal plate, and have always been diagnosed as pilocytic or low-grade astrocytomas. In our cases, the lesions could be related to so-called pencil glioma, sometimes associated with type 1 neurofibromatosis and, to our knowledge, have never been described prior to birth. The occurrence during fetal life and the progressive maturation of the nodules are more likely in favor of a hamartomatous process. CONCLUSION: Even though they could sporadically occur, an accurate genetic counseling should be required in order to ensure that there is no familial history of Recklinghausen disease, and to provide a more precise evaluation of recurrence risk.

Angiotensin II: dependence of hormone affinity on the electronegativity of a single side chain.

Structure-activity studies on rabbit aorta of angiotensin II analogues have suggested a possible relationship between the electronegativity of the aromatic side chain in position 4 (Tyr) and the observed affinity. In order to test this hypothesis, several other analogues modified in position 4 have been prepared, and all available analogues were tested in three bioassays: in vitro on rabbit aorta strip, in vivo on the rat blood pressure, and the binding assay on beef adrenocortical membranes. In all three bioassays the postulated correlation has confirmed that angiotensin II affinity depends inversely on the electronegativity of the aromatic side chain in position 4.

Molecular analysis of 53 fragile X families with the probe StB12.3.

Fifty-three pedigrees with the fragile X syndrome have been studied for amplification of the CGG repeat sequence adjacent to the CpG island in the FMR1 gene. Probe StB12.3 allowed direct detection of affected males, carrier females, normal transmitting males, as well as prenatal diagnosis. Comparison of our molecular data with our previous linkage data from 38 families indicates the effectiveness of direct DNA analysis. A total of 325 individuals were studied and no new mutation was found. All daughters of males with a premutation had a premutation. When the mother had a full mutation no children had a premutation. In premutated mothers, the size of the premutation seems to be a determining factor for the transition to the full mutation. All affected males had a full mutation or mosaicism and only 42% of the females with a full mutation were mentally impaired. Analysis of large families over 3 generations illustrated clearly the Sherman paradox. Furthermore, the analysis of these families is in reasonable agreement with the multiallelic model of Morton and Macpherson [Proc Natl Acad Sci USA 89:4215-4217, 1992]. Mosaic cases in the offspring of the mothers with a full mutation suggest a maternal germinal mosaicism. Then an abnormal methylation and a somatic heterogeneity established in very early steps of embryogenesis could explain these cases.

Isolation and characterization of histogranin, a natural peptide with NMDA receptor antagonist activity.

Histogranin, was co-purified with bombesin-like immunoreactive peptides from bovine adrenal medulla. Its structure, H-Met-Asn-Tyr-Ala-Leu-Lys-Gly-Gln-Gly-Arg-Thr-Leu-Tyr-Gly-Phe-COOH, was determined by gas-phase Edman degradation. It was in accordance with its amino acid composition and corresponded to a 15 amino acid fragment (fragment 86-100) of histone H4 with substitutions in positions 1 (Val), 2 (Val) and 7 (Arg). The peptide was synthesized by the solid-phase procedure and the synthetic product was identical to the natural peptide as determined by its retention time on three analytical high-performance liquid chromatography systems. An antibody was raised against synthetic [Ser1]histogranin and used to monitor the presence of histogranin in various rat tissues and subcellular fractions of bovine adrenal medulla. In rats, immunoreactive histogranin was mainly concentrated in the pituitary (5065 pmol/g) and the adrenal glands (268 pmol/g), but it was also present in other tissues including the brain (1.6 pmol/g) and blood plasma (24 fmol/ml). A neuropeptide function for the adrenal peptide was suggested by its relative high concentration in chromaffin granules (42 fmol/mg protein as compared with 1 fmol/mg protein in cytosol) and its release from perfused bovine adrenal glands. In rat brain membrane preparations, synthetic histogranin displaced the binding of [3H]CGP 39653, a specific ligand of N-methyl-D-aspartate (NMDA) receptor. The displacement curve was biphasic with IC50 of 0.6 and 3955 nM, representing 33% and 67% of the binding sites, respectively. Intracerebroventricular (i.c.v.) injection of the peptide (5-100 nmol) in mice produced a dose-dependent protection against NMDA (0.5-1.0 nmol) -induced convulsions but not against (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA, 0.25-2.0 nmol), kainate (0.25-0.75 nmol) and bicuculline (1-10 nmol)-induced convulsions. These results suggest that histogranin may be an endogenous modulator of NMDA receptor functions.

Apert syndrome, an antenatal ultrasound detected case.

Apert's syndrome or acrocephalosyndactyly type I is an autosomal dominant craniosynostosis syndrome with abnormalities of the hands and feet. Most cases occur as new mutations. Mental retardation is frequent because of central nervous system abnormalities. A case of Apert's syndrome detected by antenatal ultrasound examination is reported by the authors.

[Evaluation of the incidence of anencephaly and spina bifida in Brittany (1975-1984)]. / Evaluation de l'incidence de l'anencéphalie et du spina bifida en Bretagne (1975-1984).

Brittany is celtic, like Ireland and Wales where the incidence of neural tube defects is raised. We searched the hospital files in Brittany for all live and still births, and terminations of pregnancy after prenatal diagnosis for the years 1975-1984. 225 cases of spina bifida and 210 cases of anencephaly were identified; giving an incidence of 0.60 per 1000 births for spina bifida and 0.56 per 1000 births for anencephaly. No seasonality was found for both malformations. Analysis of the sex ratio for anencephaly indicated significantly higher proportion of females to males. Maternal age in the affected group was similar to the normal population. Casual heterogeneity among neural tube defects patients was presumed because 14% of our cases had other congenital anomalies.

[The CHARGE association]. / L'association CHARGE.

The CHARGE association is a polymalformative disease associating coloboma, heart disease, atresia of choanae, retarded growth and development, genital hypoplasia and ear anomalies, CHARGE being an acronym based on these different malformations. The diagnosis requires at least four of these malformations including necessarily coloboma and/or atresia of choanae. The various clinical aspects, the genetics and the therapeutics implications are described.