European journal of human genetics : EJHG
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Eur. J. Hum. Genet. · Jan 2016
Chromosomal microarray testing in adults with intellectual disability presenting with comorbid psychiatric disorders.
Chromosomal copy-number variations (CNVs) are a class of genetic variants highly implicated in the aetiology of neurodevelopmental disorders, including intellectual disabilities (ID), schizophrenia and autism spectrum disorders (ASD). Yet the majority of adults with idiopathic ID presenting to psychiatric services have not been tested for CNVs. We undertook genome-wide chromosomal microarray analysis (CMA) of 202 adults with idiopathic ID recruited from community and in-patient ID psychiatry services across England. ⋯ Furthermore deletions at 2q13, 12q21.2-21.31 and 19q13.32, and duplications at 4p16.3, 13q32.3-33.3 and Xq24-25 were observed. Routine CMA in ID psychiatry could uncover ~11% new genetic diagnoses with potential implications for patient management. We advocate greater consideration of CMA in the assessment of adults with idiopathic ID presenting to psychiatry services.
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Eur. J. Hum. Genet. · Jun 2015
Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome.
Intellectual disability (ID) has an estimated prevalence of 2-3%. Due to its extreme heterogeneity, the genetic basis of ID remains elusive in many cases. Recently, whole exome sequencing (WES) studies revealed that a large proportion of sporadic cases are caused by de novo gene variants. ⋯ In silico domain prediction of SETD5, a predicted SET domain-containing histone methyltransferase (HMT), substantiated the presence of a SET domain and identified a novel putative PHD domain, strengthening a functional link to well-known histone-modifying ID genes. All six patients presented with ID and certain facial dysmorphisms, suggesting that SETD5 sequence variants contribute substantially to the microdeletion 3p25.3 phenotype. The present report of two SETD5 LoF variants in 301 patients demonstrates a prevalence of 0.7% and thus SETD5 variants as a relatively frequent cause of ID.
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Eur. J. Hum. Genet. · Jun 2015
Rethinking biobanking and translational medicine in the Netherlands: how the research process stands to matter for patient care.
Biobanking has been identified as one of the key components of translational medicine, and while current models for translation tend to focus their attention on how the products of research projects are fed back into health-care practices, we suggest that in addition to that the research process itself can have beneficial effects on the delivery of high-quality health care by streamlining diagnostic and follow-up protocols, reduced patient waiting times, and facilitating data comparison across patients. This Viewpoint is based on experiences with, and observations of, the neurodegenerative component of a clinical biobanking initiative in the Netherlands called the Parelsnoer Institute (PSI), which links all eight of the University Medical Centers for harmonized and standardized collection and storage processes for multiple disease conditions.
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Eur. J. Hum. Genet. · Mar 2015
Role of TNF block genetic variants in HIV-associated sensory neuropathy in black Southern Africans.
HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection. The TNF block is a region within the central MHC that contains many immunoregulatory genes. Polymorphisms and haplotypes of the TNF block have been associated with increased risk of HIV-SN in Asians and whites. ⋯ One haplotype (FV18_ext1), not containing these alleles, was associated with increased risk of HIV-SN after correction for age, height and multiple comparisons. Our results confirm the involvement of genes in the TNF block in altering risk for HIV-SN, but genotypes critical in this African population differed from those affecting HIV-SN in whites and Asians. These differences support the need for genetic association studies in diverse populations.
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Eur. J. Hum. Genet. · Feb 2015
Dynamic consent: a patient interface for twenty-first century research networks.
Biomedical research is being transformed through the application of information technologies that allow ever greater amounts of data to be shared on an unprecedented scale. However, the methods for involving participants have not kept pace with changes in research capability. In an era when information is shared digitally at the global level, mechanisms of informed consent remain static, paper-based and organised around national boundaries and legal frameworks. ⋯ The technical architecture of DC includes components that can securely encrypt sensitive data and allow participant consent preferences to travel with their data and samples when they are shared with third parties. In addition to improving transparency and public trust, this system benefits researchers by streamlining recruitment and enabling more efficient participant recontact. DC has mainly been developed in biobanking contexts, but it also has potential application in other domains for a variety of purposes.