The penetrance of a genetic disorder is the risk for disease onset, given the disease-causing mutation. Heritable pulmonary arterial hypertension (PAH) is a rare genetic disorder characterised by mutations mostly occurring in the bone morphogenetic protein receptor type 2 (BMPR2) gene, and a wide heterogeneity of penetrance modifier mechanisms. In this study, we genotyped 32 […]
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Review of the scientific evolution of gene therapy for the treatment of homozygous familial hypercholesterolaemia: past, present and future perspectives
Familial hypercholesterolaemia (FH) is a devastating disease that leads to extremely high cholesterol levels and severe cardiovascular disease. The severe homozygous variety (HoFH) is not successfully treated with standard cholesterol-lowering therapies. Because HoFH is mainly due to mutations in the LDLR, this disease has been proposed as an ideal candidate for gene therapy. Several preclinical […]
Evidence for Heightened Genetic Instability in Precancerous Spasmolytic Polypeptide Expressing Gastric Glands
Spasmolytic polypeptide expressing metaplasia (SPEM) is present in more than 90% of resected gastric cancer tissues. However, although widely regarded as a pre-cancerous tissue, its genetic characteristics have not been well studied. In this work, we show for the first time that elevated genetic instability is a critical property of SPEM cells (TFF2 positive cells […]
Clinical characteristics of patients with colorectal cancer with double somatic mismatch repair mutations compared with Lynch syndrome
Colorectal cancer (CRC) patients with mismatch repair-deficient (dMMR) tumors without MLH1 methylation or germline MMR pathogenic variants (PVs) were previously thought to have Lynch syndrome (LS). It’s now appreciated that they can have double somatic (DS) MMR PVs. We explored clinical characteristics between patients with DS tumors and LS in two population-based cohorts (Ohio 2013-2016, […]
Mutations in NLRP2 and NLRP5 cause female infertility characterised by early embryonic arrest
Successful human reproduction requires normal spermatogenesis, oogenesis, fertilization, and early embryonic development, and abnormalities in any of these processes will result in infertility. Early embryonic arrest is commonly observed in infertile patients with recurrent failure of assisted reproductive technology (ART). However, the genetic basis for the phenotype is largely unknown. In this study, we identified […]
Alternative Splicing and ACMG-AMP-2015 Based Classification of PALB2 Genetic Variants: an ENIGMA Report
Carriers of germ-line defects in PALB2 have breast cancer risk estimates overlapping those of BRCA2, and recommendations for risk reduction strategies are similar. Therefore, developing standardized criteria to identify pathogenic variants in PALB2 without incurring overprediction is of paramount clinical relevance. Here, the ENIGMA consortium shows that comprehensive characterization of naturally occurring alternative splicing assists in this task by identifying […]
A Promising Member of the Short Interspersed Nuclear Elements-Alu Elements: Mechanisms and Clinical Applications in Human Cancers
This article summarized the DNA genetic modification and RNA regulation mechanism of Alu elements in tumor development, and discuss the latest clinical applications, so as to put forward advices for subsequent studies and summarize new ideas for tumorigenesis and further gene therapy. Alu elements are abundant repetitive sequence, which account for 10% of the human […]
Genetic landscape of Rett syndrome-like phenotypes revealed by whole exome sequencing
Rett syndrome (RTT) is a neurodevelopmental disorder which is mainly caused by pathogenic variants in MECP2. Whole exome sequencing of 77 patients (including typical, atypical RTT and RTT-like) without MECP2 variants achieved positive pathogenic variants in 61.0% of cases (single nucleotide variants; 50.6% and copy number variations; 10.4%). Moreover, we provided possible pathogenic variants in […]
NAA10 polyadenylation signal variants cause syndromic microphthalmia
Polyadenylation signals direct the cleavage and polyadenylation of messenger RNA (mRNA). While it is known that polyadenylation is an important process for mRNA stability and function few polyadenylation signal variants have been identified as causative for human disease. Here we identify three distinct, novel variants in the polyadenylation signal of the NAA10 gene in three […]
Natural history of renal tumours in von Hippel-Lindau disease: A large retrospective study of Chinese patients
Renal cell carcinomas (RCCs) are the most common malignant tumor in Von Hippel-Lindau (VHL) disease, which is an inherited, autosomal dominant syndrome manifested by a variety of benign and malignant tumours. The major treatment is protect as much renal function as possible while avoiding metastasis. However, proper operative strategies are unclear. Therefore, we tracked the […]