16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 × 10−6, odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10−4). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical R

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

Array-CGH detection of a de novo 0.8Mb deletion in 19q13.32 associated with mental retardation, cardiac malformation, cleft lip and palate, hearing loss and multiple dysmorphic features.

We report on a 28-year old woman carrying a 0.8Mb de novo interstitial deletion in 19q13.32 detected by high-resolution array-CGH. She has severe mental retardation, tetralogy of Fallot, cleft lip and palate, deafness, megacolon and other dysmorphic features. Only a few cases of constitutional deletions located at the long arm of chromosome 19 have been previously described and this is the first report involving 19q13.32. The deleted region encompasses 15 genes, among which 3 candidate genes for genotype-phenotype correlation could be delineated. Since SLC8A2 is broadly expressed in brain and plays a potential role during embryonic development, its haploinsufficiency could possibly be related to mental retardation; as it is also expressed in aortic and intestinal smooth muscles, SLC8A2 could be related to the aortic defect of the complex cardiac malformation and to the megacolon. SAE1, a SUMO-1 activating enzyme subunit, may be related to cleft lip and palate. KPTN coding region may be a candidate gene for hearing loss. Further experimental studies on either in vivo models or diagnostic materials are needed to elucidate the role of these potential candidate genes for the phenotypic abnormalities observed in the investigated patient

A 5.3Mb deletion in chromosome 18q12.3 as the smallest region of overlap in two patients with expressive speech delay.

Interstitial 18q deletions encompassing band 18q12.3 define the del(18)(q12.2q21.1) syndrome. Usual manifestations are mild dysmorphic features, mental retardation, behaviour abnormalities and lack of serious malformation. Seizures have also been found. Recently, more specifically, impairment of expressive language has been reported. We report on two patients with de novo 18q interstitial deletions characterized by oligonucleotide array CGH. The smallest, a 5.3Mb deletion (35.7-40.9Mb) within band q12.3, was found in a 4-year-old girl who suffered mainly from expressive dysphasia. A larger 9.5Mb deletion (34.6-43.9Mb) was observed in a 20-year-old man with a more severe clinical picture including seizures and limited speech. Among the four genes located in the 5.3Mb region, RIT2 (Ras-like without CAAX 2) and SYT4 (synaptotagmin IV), both strongly expressed in the brain, are pointed out as likely candidate genes for language development

Morphology of QSOs-the gridpoints of the Gaia Celestial Reference Frame

International audienceThe acronym QSO refers to the particular time in the life of giant galaxies, often elliptic ones, when the nucleus becomes extremely active fueled by matter infalling onto the accretion disk feeding the massive central black hole. But the duration and intensity of such a phase make QSOs to be treated as a class of objects, and indeed a c lass of enhanced cosmologic, astrophysical and astrometric bearings. As a consequence, even in the optical domain, the morphology of a quasar can be understood as comprehending the domineering central source, the immediate surrounding regions, the jet basis and features along the jet, and a bright host galaxy which is likely to be intensely star forming and generally speaking a lively place in itself. Morphology, and its color dependent aspects, can thus inform on the physical processes at work on a given Q SO, for example what is likeness to exhibit different time scales of variability. The ESA Gaia mission will have its fundamental reference frame formed by quasars, which are desired to be as point like as can be gathered for the sake of ensuring maximum astrometric precision and accuracy. We will present how the morphology characteristic is indicated in the Gaia Initial QSO Catalog and the related investigations. We will also outline t he Gaia extended sources methods that will be applied to all QSOs observe d, and the vast amount of information that will be made available from the mission outcomes

Morphology of QSOs-the gridpoints of the Gaia Celestial Reference Frame

International audienceThe acronym QSO refers to the particular time in the life of giant galaxies, often elliptic ones, when the nucleus becomes extremely active fueled by matter infalling onto the accretion disk feeding the massive central black hole. But the duration and intensity of such a phase make QSOs to be treated as a class of objects, and indeed a c lass of enhanced cosmologic, astrophysical and astrometric bearings. As a consequence, even in the optical domain, the morphology of a quasar can be understood as comprehending the domineering central source, the immediate surrounding regions, the jet basis and features along the jet, and a bright host galaxy which is likely to be intensely star forming and generally speaking a lively place in itself. Morphology, and its color dependent aspects, can thus inform on the physical processes at work on a given Q SO, for example what is likeness to exhibit different time scales of variability. The ESA Gaia mission will have its fundamental reference frame formed by quasars, which are desired to be as point like as can be gathered for the sake of ensuring maximum astrometric precision and accuracy. We will present how the morphology characteristic is indicated in the Gaia Initial QSO Catalog and the related investigations. We will also outline t he Gaia extended sources methods that will be applied to all QSOs observe d, and the vast amount of information that will be made available from the mission outcomes

Morphology of QSOs-the gridpoints of the Gaia Celestial Reference Frame

International audienceThe acronym QSO refers to the particular time in the life of giant galaxies, often elliptic ones, when the nucleus becomes extremely active fueled by matter infalling onto the accretion disk feeding the massive central black hole. But the duration and intensity of such a phase make QSOs to be treated as a class of objects, and indeed a c lass of enhanced cosmologic, astrophysical and astrometric bearings. As a consequence, even in the optical domain, the morphology of a quasar can be understood as comprehending the domineering central source, the immediate surrounding regions, the jet basis and features along the jet, and a bright host galaxy which is likely to be intensely star forming and generally speaking a lively place in itself. Morphology, and its color dependent aspects, can thus inform on the physical processes at work on a given Q SO, for example what is likeness to exhibit different time scales of variability. The ESA Gaia mission will have its fundamental reference frame formed by quasars, which are desired to be as point like as can be gathered for the sake of ensuring maximum astrometric precision and accuracy. We will present how the morphology characteristic is indicated in the Gaia Initial QSO Catalog and the related investigations. We will also outline t he Gaia extended sources methods that will be applied to all QSOs observe d, and the vast amount of information that will be made available from the mission outcomes