Pediatric hearing loss is a common disorder and universal newborn hearing screening is used to aid in the early identification of children with hearing impairment. However this screening has a significant failure rate in newborns, and hearing loss may have delayed onset and be missed by newborn screening. Genetic screening of newborns for variants that […]
Latest articles
Mendelian Randomization Applied to Drug Development in Cardiovascular Disease: A Review
Observational epidemiology has implicated a wide range of biomarkers in the onset of human disease, however given that these methods are prone confounding it becomes difficult to identify causal biomarkers deserving of pharmaceutical intervention. Mendelian randomization (MR) is an emerging technique in human genetics which utilizes the power of random assignment of genetic information at […]
Neuropathy target esterase impairments cause Oliver-McFarlane and Laurence-Moon syndromes
Here, we identified recessive mutations in the PNPLA6 gene, encoding Neuropathy Target Esterase (NTE) protein, responsible for Oliver-McFarlane and Laurence-Moon syndromes in humans. Our finding expands the spectrum of PNPLA6-associated diseases to include hair abnormalities and pituitary atrophy, which can lead to intellectual disability and short stature. We further link the mechanisms among other PNPLA6-associated […]
CTNND2—a candidate gene for reading problems and mild intellectual disability
In a small subset of patients, apparently balanced structural chromosome rearrangements may associate with neurocognitive problems ranging from mild (ADHD, dyslexia) to severe (within the autism spectrum disorders and intellectual disability). Here, we use low coverage massive parallel whole genome sequencing and microarray analysis to identify hemizygous loss of CTNND2 in three individuals from two […]
Current novel-gene-finding strategy for autosomal-dominant hypercholesterolaemia needs refinement
Autosomal Dominant Hypercholesterolemia (ADH) is a heterogeneous common disorder characterized by elevated levels of plasma low-density lipoprotein (LDL-C), total cholesterol, and increased risk of cardiovascular disease. Uncovering the molecular determinants that underlie ADH is a major focus of cardiovascular research, but despite rapid technical advances, efforts to identify novel ADH genes have yet not been […]
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 […]
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 […]
Pseudogene in Cancer: Real Functions and Promising Signature
During the long history of human genome evolution, some gene loci have lost the protein-coding abilities due to various kinds of mutations. These genes are termed pseudogenes that are previously regarded as functional inert. Studies in recent decades, however, have discovered many kinds of functions pseudogenes play both in health and in disease, especially in […]
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 […]
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 […]