Long-read sequencing identified repeat expansions in the 5′UTR of the NOTCH2NLC gene from Chinese patients with neuronal intranuclear inclusion disease

Neuronal intranuclear inclusion disease (NIID) is a myth and has perplexed the neurologists for half a century, due to its high clinical heterogeneity with unknown genetic causes. This progressive neurodegenerative disease is characterized by the formation of eosinophilic hyaline intranuclear inclusions in neuronal system and multiple organs. In this article, the authors performed whole-genome sequencing […]

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Hypolipidaemia among patients with PMM2-CDG is associated with low circulating PCSK9 levels: a case report followed by observational and experimental studies

Low cholesterol is a common feature among patients with congenital disorders of glycosylation (CDG), but the exact underlying mechanisms remain unknown. We explored the role of proprotein convertase subtilisin/kexin type 9 precursor (PCSK9), a major cholesterol regulator, in mediating low cholesterol among CDG patients. First, we describe a CDG patient with low circulating PCSK9 levels. […]

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Truncating mutations in exons 20 and 21 of OFD1 can cause primary ciliary dyskinesia without associated syndromic symptoms

Ciliopathies are a group of diseases triggered by the dysfunction of primary and/or motile cilia, caused by mutations in various genes. Mutations of the X-linked OFD1 gene, which mostly influence primary cilia, cause several syndromic ciliopathies. We identified four novel OFD1 mutations in males with symptoms typical of motile cilia dysfunction (primary ciliary dyskinesia, PCD), but without severe neurological, […]

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RASA1 mosaic mutations in patients with capillary malformation – arteriovenous malformation

Capillary malformation – arteriovenous malformation is an autosomal dominant disorder, characterised by capillary malformations and an increased risk of fast-flow lesions. It is caused by mutations in two genes: RASA1 or EPHB4. Around 25% of the patients remain unexplained. In this study, we show that some of the so called “negative cases” are caused by […]

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CCMG Practice Guideline: Laboratory Guidelines for Next-Generation Sequencing

The Canadian College of Medical Geneticists (CCMG) Laboratory Guidelines for Next-Generation Sequencing position statement provides guidance for the use of NGS in Canadian clinical genetic laboratories. The guidelines cover NGS applications for detection of variants in genomic DNA and mitochondrial DNA for inherited disorders, and for somatic variants in tumour DNA for acquired cancers. Intended […]

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One in three highly selected Greek breast cancer patients carries a loss-of-function variant in a cancer susceptibility gene

Pathogenic variants in a number of genes, conferring high or moderate risks have been associated to hereditary breast cancer. Studying a highly selected cohort of 1,382 Greek breast cancer patients, 436 inherited pathogenic variants distributed in twenty-eight genes, have been identified. Beyond established associations, i.e. high breast cancer risk conferred by TP53 and PALB2 pathogenic […]

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Clinical features and cancer risk in families with pathogenic CDH1 variants irrespective of clinical criteria

Individuals with mutations in the CDH1 gene have the inherited hereditary diffuse gastric cancer syndrome. This study is the first report on cancer risk in patients with CDH1 mutations that were not previously selected from families highly suspicious for this syndrome. The results indicate that gastric cancer risks are lower and age at diagnosis higher […]

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Genetic characteristics of retinitis pigmentosa in 1,204 Japanese patients

Retinitis pigmentosa (RP) is the most common form of hereditary retinal degenerative disease worldwide. We performed large-scale high-coverage targeted resequencing of 83 causative genes of RP. The analyzed samples accounted for more than 4 % of all RP patients in Japan, leading us to reveal comprehensive characteristics of causative genes and variants in the Japanese […]

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