Life Sciences

Genetic Heterogeneity in Cornelia De Lange Syndrome (CdLS) and CdLS-like Phenotypes With Observed and Predicted Levels of Mosaicism

P.M. , e.al. , R.A. , C.J. , A.M. , B.H. , P.G. , F.Q. , W.K. , A.R. , M.A. , C.C. , K.H. , A.Ş. , H.R. , L.A. , R.E. , H.T. , S.M. , M.S. , S.M.


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Background: Cornelia de Lange syndrome (CdLS) is a multisystem disorder with distinctive facial appearance, intellectual disability and growth failure as prominent features. Most individuals with typical CdLS have de novo heterozygous loss-of-function mutations in NIPBL with mosaic individuals representing a significant proportion. Mutations in other cohesin components, SMC1A, SMC3, HDAC8 and RAD21 cause less typical CdLS. Methods: We screened 163 affected individuals for coding region mutations in the known genes, 90 for genomic rearrangements, 19 for deep intronic variants in NIPBL and 5 had whole-exome sequencing. Results: Pathogenic mutations [including mosaic changes] were identified in: NIPBL 46 [3] (28.2%); SMC1A 5 [1] (3.1%); SMC3 5 [1] (3.1%); HDAC8 6 [0] (3.6%) and RAD21 1 [0] (0.6%). One individual had a de novo 1.3 Mb deletion of 1p36.3. Another had a 520 kb duplication of 12q13.13 encompassing ESPL1, encoding separase, an enzyme that cleaves the cohesin ring. Three de novo mutations were identified in ANKRD11 demonstrating a phenotypic overlap with KBG syndrome. To estimate the number of undetected mosaic cases we used recursive partitioning to identify discriminating features in the NIPBL-positive subgroup. Filtering of the mutation-negative group on these features classified at least 18% as ‘NIPBL-like’. A computer composition of the average face of this NIPBL-like subgroup was also more typical in appearance than that of all others in the mutationnegative group supporting the existence of undetected mosaic cases. Conclusions: Future diagnostic testing in ‘mutationnegative’ CdLS thus merits deeper sequencing of multiple DNA samples derived from different tissues.Morad Ansari ... Elizabeth M Thompson ... et a

First-Episode Psychosis and Migration in Italy (PEP-Ita Migration): a Study in the Italian Mental Health Services

F.S , L.M , N.M , D.Rosa, , B.V , C.B , R.M , R.C , D.Vecchio, , F.A , A.F , L.Cascia, , T.I , B.M , B.G , B.A , C.A , C.Donati, , D.S , F.L , F.MA , B.D , G.C , M.A , P.F , P.D , T.O , T.E , V.A , Z.P


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Background: It has been frequently reported a higher incidence of psychotic disorders in immigrants than in native populations. There is, however, a lack of knowledge about risk factors which may explain this phenomenon. A better understanding of the causes of psychosis among first-generation migrants is highly needed, particularly in Italy, a country with a recent massive migration.Methods/Design: The " Italian study on first-episode psychosis and migration (PEP-Ita)" is a prospective observational study over a two-year period (1 January 2012-31 December 2013) which will be carried out in 11 Italian mental health centres. All participating centres will collect data about all new cases of migrants with first-episode psychosis. The general purpose (" core" ) of the PEP-Ita study is to explore the socio-demographic and clinical characteristics, and the pathways to care of a population of first-episode psychosis migrants in Italy. Secondary aims of the study will be: 1) to understand risk and protective factors for the development of psychotic disorders in migrants; 2) to evaluate the correlations between psychopathology of psychotic disorders in migrants and socio-demographic characteristics, migration history, life experiences; 3) to evaluate the clinical and social outcomes of first-episode psychoses in migrants.Discussion: The results of the PEP-Ita study will allow a better understanding of risk factors for psychosis in first-generation migrants in Italy. Moreover, our results will contribute to the development of prevention programmes for psychosis and to the improvement of early intervention treatments for the migrant population in Italy
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