Nonclassic lipoid congenital adrenal hyperplasia masquerading as familial glucocorticoid deficiency

Context: Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder resulting from resistance to the action of ACTH on the adrenal cortex. Affected individuals are deficient in cortisol and, if untreated, are likely to succumb to hypoglycemia and/or overwhelming infection. Mutations of the ACTH receptor (MC2R) and the melanocortin 2 receptor accessory protein (MRAP), FGD types 1 and 2 respectively, account for approximately 45% of cases. Objective: A locus on chromosome 8 has previously been linked to the disease in three families, but no underlying gene defect has to date been identified. Design: The study design comprised single-nucleotide polymorphism genotyping and mutation detection. Setting: The study was conducted at secondary and tertiary referral centers. Patients: Eighty probands from families referred for investigation of the genetic cause of FGD participated in the study. Interventions: There were no interventions. Results: Analysis by single-nucleotide polymorphism array of the genotype of one individual with FGD previously linked to chromosome 8 revealed a large region of homozygosity encompassing the steroidogenic acute regulatory protein gene, STAR. We identified homozygous STAR mutations in this patient and his affected siblings. Screening of our total FGD patient cohort revealed homozygous STAR mutations in a further nine individuals from four other families. Conclusions: Mutations in STAR usually cause lipoid congenital adrenal hyperplasia, a disorder characterized by both gonadal and adrenal steroid deficiency. Our results demonstrate that certain mutations in STAR (R192C and the previously reported R188C) can present with a phenotype indistinguishable from that seen in FGD

Sextet, piano, wind quintet

6 parts. 34 cm

Récréations philologiques, ou Recueil de notes pour servir à l'histoire des mots de la langue française,

Mode of access: Internet

Introduction à la Chanson de Roland, suivie du manuscrit de Valenciennes.

Bibliographical references.Mode of access: Internet

Die Jesuiten und die Universität /

Translation of: Les Jésuites et l'université.Cover title.Mode of access: Internet

Robustness of Case-Control Studies of Genetic Factors to Population Stratification: Magnitude of Bias and Type I Error

Abstract Case-control studies of genetic factors are prone to a special form of confounding called population stratification, whenever the existence of one or more subpopulations may lead to a false association, be it positive or negative. We quantify both the bias (in terms of confounding risk ratio) and the probability of false association (type I error) in the most unfavorable situation in which only one high-risk subpopulation is hidden within the studied population, considering different scenarios of population structuring and varying sample sizes. In accord with previous work, we find that the bias is likely to be small in most cases. In addition, we show that the same applies to the associated type I error whenever the subpopulation is small in proportion. For instance, when the hidden subpopulation makes up 5% of the entire population, with an allelic frequency of 0.25 (versus 0.10) and a disease rate that is double, then the estimated bias is 1.07 and the type I error associated with a sample of 500 cases and 500 controls is 8% (instead of 5%). We also show that the type I error is substantially greater for a rare allele (frequency of 0.1) than for a common allele (frequency of 0.5) and analyze the pattern of increase of vulnerability to stratification bias with sample size. Based on our findings, we may therefore conclude that with moderate sample sizes the type I error associated with population stratification remains very limited in most realistic scenarios.</jats:p

Identification of New Natural Sweet Compounds in Wine Using Centrifugal Partition Chromatography–Gustatometry and Fourier Transform Mass Spectrometry

Sweetness contributes notably to the taste-balance of dry wines and increases during oak-barrel aging owing to the release of natural sweeteners from wood. The search for such taste-active molecules, which are sometimes present at very low concentrations in wine or other complex matrixes, requires both reliable purification tools and powerful identification techniques. Here, we report the development of an original inductive method using centrifugal partition chromatography (CPC) and sensorial analysis. This method, called CPC–gustatometry, was implemented to isolate a sweet fraction with only four compounds from a complex oak wood extract. The recently developed Fourier transform mass spectrometry (FT-MS, Orbitrap analyzer) was used jointly with two-dimensional nuclear magnetic resonance (2D 1H and 13C NMR) to obtain the structural elucidation of the purified compounds. The tandem mass spectrometry (MS/MS) spectra obtained with resonant and nonresonant fragmentation modes were compared, thus providing complementary information about the molecular structure. Two oleanane-type triterpenoids substituted with galloyl and glucosyl moieties were identified, one of which exhibits sweet properties. We term these compounds which have never been reported, Quercotriterpenoside I and II

Nouvelles lettres de la reine de Navarre, addressées au roi François Ier, son frère /

Mode of access: Internet