Synchronized long-read genome, methylome, epigenome, and transcriptome for resolving a Mendelian condition.

Resolving the molecular basis of a Mendelian condition (MC) remains challenging owing to the diverse mechanisms by which genetic variants cause disease. To address this, we developed a synchronized long-read genome, methylome, epigenome, and transcriptome sequencing approach, which enables accurate single-nucleotide, insertion-deletion, and structural variant calling and diploid genome assembly, and permits the simultaneous elucidation of haplotype-resolved CpG methylation, chromatin accessibility, and full-length transcript information in a single long-read sequencing run. Application of this approach to an Undiagnosed Diseases Network (UDN) participant with a chromosome X;13 balanced translocation of uncertain significance revealed that this translocation disrupted the functioning of four separate genes (, , , and ) previously associated with single-gene MCs.

HUWE1 variants cause dominant X-linked intellectual disability: a clinical study of 21 patients.

Whole-gene duplications and missense variants in the HUWE1 gene (NM_031407.6) have been reported in association with intellectual disability (ID). Increased gene dosage has been observed in males with non-syndromic mild to moderate ID with speech delay.

encephalopathy: A new disease of vesicle fission.

Objective: To evaluate the phenotypic spectrum caused by mutations in dynamin 1 (), encoding the presynaptic protein DNM1, and to investigate possible genotype-phenotype correlations and predicted functional consequences based on structural modeling.

Methods: We reviewed phenotypic data of 21 patients (7 previously published) with mutations. We compared mutation data to known functional data and undertook biomolecular modeling to assess the effect of the mutations on protein function.

Recurrent duplications of 17q12 associated with variable phenotypes.

The ability to identify the clinical nature of the recurrent duplication of chromosome 17q12 has been limited by its rarity and the diverse range of phenotypes associated with this genomic change. In order to further define the clinical features of affected patients, detailed clinical information was collected in the largest series to date (30 patients and 2 of their siblings) through a multi-institutional collaborative effort. The majority of patients presented with developmental delays varying from mild to severe.

Direct medical cost of newly diagnosed stable coronary artery disease in Hong Kong.

Background: Stable coronary artery disease (CAD) affects approximately 7% of the population of Hong Kong and is associated with substantial healthcare costs.

Objective: We aimed to evaluate the first-year direct medical cost for a patient with newly diagnosed stable CAD at a tertiary care public hospital in Hong Kong and to identify CAD-related resource consumption pattern among different patient subgroups.

Methods: 89 consecutive patients with newly diagnosed stable CAD at our institution from January 2007 to December 2009 were retrospectively analysed.

Methylglyoxal-modified collagen promotes myofibroblast differentiation.

Fibrosis is a frequent complication of diabetes mellitus in many organs and tissues but the mechanism of how diabetes-induced glycation of extracellular matrix proteins impacts the formation of fibrotic lesions is not defined. As fibrosis is mediated by myofibroblasts, we investigated the effect of collagen glycation on the conversion of human cardiac fibroblasts to myofibroblasts. Collagen glycation was modeled by the glucose metabolite, methylglyoxal (MGO).

A new helper phage and phagemid vector system improves viral display of antibody Fab fragments and avoids propagation of insert-less virions.

Phage display technology (PDT) is a powerful method for isolating functional gene products such as antigen-specific monoclonal antibodies (mAbs). To improve the effectiveness of PDT, we sought to optimize display of Fab-g3p (antibody fragment fused with viral gene 3 protein) on phagemid virions and to optimize the yield of such phage. To do so, we constructed a novel helper phage, Phaberge, having a conditional deficiency in g3p production.