Prevention of HIV and Associated Infections among Adolescents and Young People at High Risk of Infection : Methodology Guide

Methodology Guide on Prevention of HIV and Associated Infections among Adolescents and Young People at High Risk of Infection was prepared as part of project “Building capacity in prevention of HIV and associated infections among youth at high risk in the Northern Dimension area” (cf. www.ndphs.org/?database,view,project,1467) co-funded by the European Union. The project was implemented from September 1, 2013 to August 31, 2015 by the project consortium led by Secretariat of the Northern Dimension Partnership in Public Health and Social Well-being (NDPHS) and including also Regional NGO “Stellit”, National Institute for Health and Welfare, Kaliningrad Regional Non-governmental Youth Organisation “Young Leaders Army” (YLA), Social AIDS Committee and Baltic HIV Association. The Methodology Guide contains overview of theories applicable for addressing the priorities of HIV and associated infections prevention among adolescents and young people at high risk of infection, theories which might be used to evaluate the effectiveness of prevention programs. It provides the results of assessment of needs of children and young people at high risk of infection in prevention programs, overview of prevention programs implemented in Russia, Latvia, Poland, Finland and Germany which might be recommended to be spread to other countries of the NDPHS and examples of tool which might be used in prevention work. The Methodology Guide might be useful for authorities, representatives of governmental organizations, NGOs, international organizations, public health specialists and other experts involved into HIV and associated infections prevention among children and young people. The Methodology Guide is available for downloading at: http://urn.fi/URN:NBN:fi-fe2015102715069. Other methodological materials produced within the project can be downloaded at: https://www.thl.fi/en/web/thlfi-en/about-us/organisation/departments-and-units/administration-and-development/planning/international-affairs-unit/projects

Exome sequencing identifies pathogenic variants of VPS13B in a patient with familial 16p11.2 duplication

BACKGROUND: The recurrent microduplication of 16p11.2 (dup16p11.2) is associated with a broad spectrum of neurodevelopmental disorders (NDD) confounded by incomplete penetrance and variable expressivity. This inter- and intra-familial clinical variability highlights the importance of personalized genetic counselling in individuals at-risk. CASE PRESENTATION: In this study, we performed whole exome sequencing (WES) to look for other genomic alterations that could explain the clinical variability in a family with a boy presenting with NDD who inherited the dup16p11.2 from his apparently healthy mother. We identified novel splicing variants of VPS13B (8q22.2) in the proband with compound heterozygous inheritance. Two VPS13B mutations abolished the canonical splice sites resulting in low RNA expression in transformed lymphoblasts of the proband. VPS13B mutation causes Cohen syndrome (CS) consistent with the proband’s phenotype (intellectual disability (ID), microcephaly, facial gestalt, retinal dystrophy, joint hypermobility and neutropenia). The new diagnosis of CS has important health implication for the proband, provides the opportunity for more meaningful and accurate genetic counselling for the family; and underscores the importance of longitudinally following patients for evolving phenotypic features. CONCLUSIONS: This is the first report of a co-occurrence of pathogenic variants with familial dup16p11.2. Our finding suggests that the variable expressivity among carriers of rare putatively pathogenic CNVs such as dup16p11.2 warrants further study by WES and individualized genetic counselling of families with such CNVs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-016-0340-0) contains supplementary material, which is available to authorized users

Changing facial phenotype in Cohen syndrome:towards clues for an earlier diagnosis

<p>Cohen syndrome (CS) is a rare autosomal recessive condition caused by mutations and/or large rearrangements in the VPS13B gene. CS clinical features, including developmental delay, the typical facial gestalt, chorioretinal dystrophy (CRD) and neutropenia, are well described. CS diagnosis is generally raised after school age, when visual disturbances lead to CRD diagnosis and to VPS13B gene testing. This relatively late diagnosis precludes accurate genetic counselling. The aim of this study was to analyse the evolution of CS facial features in the early period of life, particularly before school age (6 years), to find clues for an earlier diagnosis. Photographs of 17 patients with molecularly confirmed CS were analysed, from birth to preschool age. By comparing their facial phenotype when growing, we show that there are no special facial characteristics before 1 year. However, between 2 and 6 years, CS children already share common facial features such as a short neck, a square face with micrognathia and full cheeks, a hypotonic facial appearance, epicanthic folds, long ears with an everted upper part of the auricle and/or a prominent lobe, a relatively short philtrum, a small and open mouth with downturned corners, a thick lower lip and abnormal eye shapes. These early transient facial features evolve to typical CS facial features with aging. These observations emphasize the importance of ophthalmological tests and neutrophil count in children in preschool age presenting with developmental delay, hypotonia and the facial features we described here, for an earlier CS diagnosis.</p>