Hereditary hemochromatosis (HH) caused by a homozygous p.C282Y mutation in hemochromatosis (HFE) gene has been well-documented in Caucasian patients with HH. However, the morbidity of HH is less reported in Asian countries. Little is known about the general patterns of mutation of HH-related gene in Chinese patients. The present study by Lv et al. provided […]
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Perturbations of BMP/TGF-β and VEGF/VEGFR signalling pathways in non-syndromic sporadic brain arteriovenous malformations (BAVM)
Brain arteriovenous malformations (BAVM) represent a congenital anomaly of the cerebral vessels with a prevalence of 10–18/100,000. BAVM is the leading etiology of intracranial hemorrhage in children. To identify gene variants potentially contributing to disease, we sequenced the DNA of 100 families with a BAVM phenotype. Pathogenic variants were then studied in vivo using a […]
Homozygous variants in KIAA1549, encoding a ciliary protein, are associated with autosomal recessive retinitis pigmentosa
Retinitis pigmentosa (RP) is a genetically inherited eye disease, and is the most frequent cause of inherited blindness worldwide. More than 80 genes have been identified in which defects can cause RP, although in approximately 20-40% of the patients still no genetic explanation can be found. In this study, we have associated genetic defects in […]
Whole-genome sequencing analysis of CNV using low-coverage and paired-end strategies is efficient and outperforms array-based CNV analysis
Stanford researchers show that whole-genome sequencing (WGS) can replace microarrays for detecting copy-number variants (CNVs) in the human genome – by sequencing the samples at low coverage using benchtop next-generation DNA sequencers. Microarrays are the current standard for CNV detection in clinical diagnostics for birth defects, brain disorders, or cancer, and also in stem cell […]
Rapid Paediatric Sequencing (RaPS): comprehensive real-life workflow for rapid diagnosis of critically ill children
To enable optimal care, critically ill children on intensive care units (ICU)s may benefit from rapid genetic diagnosis. We developed a workflow incorporating whole genome sequencing and causal variant identification in as little as 4 days. We investigated 24 individuals with suspected rare diseases on ICU at Great Ormond Street Hospital using this workflow. We […]
XRCC2 mutation causes meiotic arrest, azoospermia and infertility
In most eukaryotes, meiotic homologous recombination (HR) is mediated by two recombinase systems, namely, the ubiquitous RAD51 and meiosis-specific DMC1. In the RAD51-mediated HR system, five paralogs are essential for normal RAD51 function. Meanwhile, given the embryonic lethality of RAD51 or any RAD51 paralog knockouts, the role of RAD51 in mammalian meiosis is unclear. This […]
Evolution of genetic assessment for BRCA-associated gynaecologic malignancies: a Canadian multisociety roadmap
BRCA1/2 gene mutations are inherited from a parent or acquired in the cells of a tumour. With advances in personalized cancer treatment, knowledge BRCA1/2 mutations (inherited or acquired) can direct cancer treatment, particularly ovarian cancer. This has increased requests for multiple types genetic testing, requiring changes to current genetic testing models. Led by the Society […]
Bacteria-free minicircle DNA system to generate integration-free CAR-T cells
Chimeric antigen receptor T (CAR-T) cells engineered with viral vectors have been successfully applied to treat patients with B cell malignancy. However, viral integration has the potential risk of mutagenesis, and the efforts and cost of viral vector production are demanding. Using non-integrative episomal vector to generate integration free CAR-T cells is an attractive option. […]
Paternal uniparental disomy of chromosome 19 in a pair of monochorionic diamniotic twins with dysmorphic features and developmental delay
Uniparental disomy (UPD) occurs when a person obtains both copies of the homologous chromosome from one parent. UPD can be associated with human diseases caused by disruption of genomic imprinting or homozygosity for a recessive trait. In this report, we describe the first human case of paternal UPD for chromosome 19 in monozygotic twins showing […]
Fine mapping MHC associations in Graves’ disease and its clinical subtypes in Han Chinese
The classical human leukocyte antigen (HLA) genes were the most important genetic determinant for Graves’ disease (GD). We applied imputation to thoroughly investigate the MHC associations with GD down to the amino acid level of classical HLA genes in 1,468 GD patients and 1,490 controls of Han Chinese. We observed the top association signal at […]