Exhaustive methylation analysis revealed uneven profiles of methylation at IGF2/ICR1/H19 11p15 loci in Russell Silver syndrome

The imprinted 11p15 IGF2/ICR1/H19 domain contains ten differentially methylated loci all methylated on the paternal allele. Hypomethylation at this domain causes Russell Silver Syndrome (RSS), a condition associating severe growth retardation, metabolic disturbances and characteristic dysmorphism. We have exhaustively documented the methylation pattern across the entire IGF2/ICR1/H19 domain in a large cohort of RSS patients […]

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Next-generation sequencing of nine atrial fibrillation candidate genes identified novel de novo mutations in patients with extreme trait of atrial fibrillation

Atrial fibrillation (AF) is the most common arrhythmia and a hereditary disease. AF may be caused by the joint effect of many or several common genetic variations or variants. Genome-wide association studies (GWAS) have identified common genetic variants in several genes associated with AF. Recent studies also suggest that rare genetic variants or mutations may […]

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Differential increase of specific FMR1 mRNA isoforms in premutation carriers

RNA toxicity due to increased FMR1 mRNA levels observed in premutation carriers is the leading molecular mechanism proposed for FMR1 associated disorders. Our analysis comparing premutation carriers and control samples suggests that RNA toxicity may arise from increased expression levels of all FMR1 mRNA isoforms. In addition, Iso10 and Iso10b transcripts, which lack important functional […]

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MUTATIONS IN THE TRICARBOXYLIC ACID CYCLE ENZYME, ACONITASE 2, CAUSE EITHER ISOLATED OR SYNDROMIC OPTIC NEUROPATHY WITH ENCEPHALOPATHY AND CEREBELLAR ATROPHY

Inherited optic neuropathy can be isolated or syndromic and are associated with mutations in genes encoding proteins involved in various mitochondrial functions. We identified mutations in ACO2 encoding the mitochondrial aconitase, an enzyme of the tricarboxylic acid cycle, in five patients with optic atrophy isolated or associated with severe neurological signs. By using a yeast […]

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International requirements for consent in biobank research. Qualitative review of research guidelines

It is uncontroversial that, if any possible, biobank researcher should seek consent from the individuals whose biomaterials they use. However, a gold standard for consent procedures in Biobank research does not yet exist. Also research guidelines do not explicitly mention all potentially relevant issues for consent in biobank research. Based on a qualitative review of […]

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Clinical, histological and genetic characterization of patients with tubular aggregate myopathy caused by mutations in STIM1

Tubular aggregate myopathies (TAM) are progressive muscle disorders characterized by abnormal accumulations of densely packed membrane tubules on biopsies. The implicated gene STIM1 controls intracellular calcium balance and plays an important role in the regulation of muscle contraction. Here we describe patients with new STIM1 mutations clustering the calcium-binding domain and impairing normal protein function. […]

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OTX2 mutations cause autosomal dominant pattern dystrophy of the retinal pigment epithelium

Pattern dystrophy (PD) of the retinal pigment epithelium is a slowly progressive genetically heterogeneous autosomal dominant disorder. As the name suggests, the disease manifests as changes in the retina that display a certain ‘pattern’. We performed genetic analyses in two families with PD; different approaches that included linkage analysis and whole exome sequencing were used. […]

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Defining and managing incidental findings in genetic and genomic practice

Our review explored questions about the management and disclosure of incidental genomic findings—those discovered through whole-genome approaches, but unrelated to the question that was asked. We have discussed the various terms used for such findings; factors that determine disclosure; differences in clinical, research and commercial settings; and ethical/practical issues about familial implications and re-contacting testees. […]

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