Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: towards recommendation for molecular testing and management

International audienceSHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology of SHORT syndrome has permitted a reassessment of the clinical phenotype. The detailed phenotypes of 32 individuals with SHORT syndrome and PIK3R1 mutation, including eight newly ascertained individuals, were studied to fully define the syndrome and the indications for PIK3R1 testing. The major features described in the SHORT acronym were not universally seen and only half (52%) had 4 or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included IUGR \textless 10(th) percentile, postnatal growth restriction, lipoatrophy and the characteristic facial gestalt. Anterior chamber defects and insulin resistance or diabetes were also observed but were not as prevalent. The less specific, or minor features of SHORT syndrome include teething delay, thin wrinkled skin, speech delay, sensorineural deafness, hyperextensibility of joints and inguinal hernia. Given the high risk of diabetes mellitus, regular monitoring of glucose metabolism is warranted. An echocardiogram, ophthalmological and hearing assessments are also recommended

Finger creases lend a hand in Kabuki syndrome.

International audienceKabuki syndrome (KS) is a rare syndrome associating malformations with intellectual deficiency and numerous visceral, orthopedic, endocrinological, immune and autoimmune complications. The early establishment of a diagnostic of KS leads to better care of the patients and therefore prevents complications such as perception deafness, severe complications of auto-immune diseases or obesity. However, the diagnosis of KS remains difficult because based on the appreciation of facial features combined with other highly variable features. We describe a novel sign, namely the attenuation and/or congenital absence of the IPD crease of the third and fourth fingers associated with limitation of flexion of the corresponding joints, which seems to be specific of KS and could help the clinician to diagnose KS

Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation

Effects of eight neuropsychiatric copy number variants on human brain structure

Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions

Post-column addition as a method of controlling triacylglycerol response coefficient of an evaporative light scattering detector in liquid chromatography–evaporative light-scattering detection

International audienc

Évaluation de la biodiversité de quelques cucurbitacées d’Afrique subsaharienne à partir des données chromatographiques (CGC et CLHP)

Two triacylglycerol quantitative analysis methods, needing none standard, using liquid chromatography coupled with light scattering detection, as well as fatty acid methyl esters quantitative analysis using capillary gas chromatography were led. In application, seed oil saponifiable fraction composition of eight groups of cucurbitacee’s seeds from equatorial and west Africa was determinated Their correct classification and their differentiation using respectively factorial discriminent and principal component analysis were investigated. It is demonstrated that the best method for characterizing an oil is the new original triacylglycerol quantitative analysis reported in this article. The interest of the two other methods is also reported

Identification des triacylglycérols en HPLC. Comment se passer du couplage HPLC-SM ? Dans quel cas la chromatographie est-elle encore indispensable ?

Les huiles et graisses sont principalement constituées de triacylglycérols. Ces derniers diffèrent par leur nombre total de carbone, la répartition des acides gras sur les trois sommets de la tête glycéryle et la configuration linéaire, ramifiée ou cyclique des chaînes grasses. Ils diffèrent aussi par leur nombre total de doubles liaisons, leur répartition sur les chaînes grasses, et au sein d’une chaîne grasse par leur position et leur configuration. Cela conduit à des mélanges complexes comprenant un grand nombre de congénères qu’il est classique d’analyser par chromatographie en phase liquide. Dans cet article, nous montrons qu’indépendamment du détecteur utilisé (DEDL, Corona, SM) la seule utilisation des lois de rétention ln α = f(NC), ln α = f(NDL) et ln α = f(NP) permet d’identifier les triacylglycérols d’huiles d’Afrique équatoriale. La démarche proposée ne nécessite pas de couplage spécifique avec la spectrométrie de masse, un système HPLC de base suffit. À titre d’exemple nous avons choisi l’huile de Ricinodendron heudelotii qui contient majoritairement des acides gras polyinsaturés en C18:3 isomères de position et de configuration

Identification des triacylglycérols en HPLC. Comment se passer du couplage HPLC-SM ? Dans quel cas la chromatographie est-elle encore indispensable ?

Les huiles et graisses sont principalement constituées de triacylglycérols. Ces derniers diffèrent par leur nombre total de carbone, la répartition des acides gras sur les trois sommets de la tête glycéryle et la configuration linéaire, ramifiée ou cyclique des chaînes grasses. Ils diffèrent aussi par leur nombre total de doubles liaisons, leur répartition sur les chaînes grasses, et au sein d’une chaîne grasse par leur position et leur configuration. Cela conduit à des mélanges complexes comprenant un grand nombre de congénères qu’il est classique d’analyser par chromatographie en phase liquide. Dans cet article, nous montrons qu’indépendamment du détecteur utilisé (DEDL, Corona, SM) la seule utilisation des lois de rétention ln α = f(NC), ln α = f(NDL) et ln α = f(NP) permet d’identifier les triacylglycérols d’huiles d’Afrique équatoriale. La démarche proposée ne nécessite pas de couplage spécifique avec la spectrométrie de masse, un système HPLC de base suffit. À titre d’exemple nous avons choisi l’huile de Ricinodendron heudelotii qui contient majoritairement des acides gras polyinsaturés en C18:3 isomères de position et de configuration