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 […]
Latest articles
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 […]
The Contribution of Spurious Transcription to Intellectual Disability Disorders
During embryonic development, the different cell types that make our bodies activate distinct gene expression programs. But what happens when the mechanisms that regulate cell-specific gene expression fail and the cells start to express genes that should be silenced? This is a typical feature of cancer cells often associated with genomic instability. Our article proposes […]
Associations of CDH1 germline variant location and cancer phenotype in families with hereditary diffuse gastric cancer (HDGC)
Hereditary diffuse gastric cancer (HDGC) is a cancer predisposition syndrome with significantly elevated life-time risks of gastric and breast cancer due to loss-of-function (LOF) germline variants of the CDH1 gene. There is considerable variability across affected families in its clinical manifestations including age-of-onset and cancer phenotype. In this study, we identified associations between location of […]
Diagnosis of ‘possible’ mitochondrial disease: an existential crisis
Primary mitochondrial diseases remain difficult to diagnose. Many patients with a phenotype concerning for mitochondrial disease are unable to receive genetic confirmation. In these instances, diagnostic terms such as “unlikely,” “possible” or “probable” mitochondrial disease are often used. Advances in genomic testing have shown that some patients with a clinical phenotype and biochemical abnormalities suggesting […]
Clinical spectrum and pleiotropic nature of CDH1 germline mutations
The human CDH1 gene codes for E-cadherin, a cell-cell adhesion molecule that is essential for embryonic development and organization of adult epithelial tissues. Carriers of a CDH1 germline mutation have a lifetime risk of diffuse gastric cancer (DGC) of up to 80% and women have also a probability of 42% of developing lobular breast cancer […]
Longitudinal evaluation of SMN levels as biomarker for Spinal Muscular Atrophy Molecular: results of a phase-IIb double-blind study of salbutamol
Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder, due to the loss of the SMN1 gene. We have performed a 1-year placebo-controlled study with salbutamol, a compound commonly used for asthma, in SMA adult patients. Objectives of the study were the usefulness of SMN dosage in blood, and the safety of oral salbutamol. Beside […]