Sedlin and prostaglandin E2 dehydrogenase - interactions and implications for spondyloepiphyseal dysplasia tarda

Session D - Genomic Disorders: abstract no. D020Spondyloepiphyseal dysplasia tarda (SEDT) is a rare X-linked, late-onset skeletal disease. Affected individuals develop phenotypes in their early childhood, displaying barrel-shaped chests, vertebral bodies malformation, flattened disc spaces and premature osteoarthritis in weight-bearing joints. The disease was found linked to the gene SEDL coding for the protein sedlin. Sedlin is one of the subunits of the TRAPP (Transport Protein Particle) complex, which is responsible for vesicle tethering during endoplasmic reticulum-to-golgi transport. Although sedlin is known to function in intracellular trafficking, the reason why mutations in a trafficking protein lead to a skeletal disease remains unknown. To address this, four missense mutations (D47Y, S73L, F83S and V130D) of sedlin observed in SEDT patients were studied. Except D47Y, the other three mutations cause proteosomal degradation of sedlin in cultured cells, whereas the D47Y mutation had a minor effect on Bet3 binding to sedlin. Pull-down assay was performed to identify novel sedlin interacting partners. 15-hydroxyprostaglandin dehydrogenase (PGDH) was pulled down and the interaction was confirmed in cell culture system. Sedlin activates PGDH activity in vitro. By confocal microscopy, sedlin was also found to colocalize with PGDH in the cytosol. PGDH catalyzes the degradation of prostaglandin E2, which affects cartilage and bone growth. Further investigation is ongoing to understand the function of sedlin and the mechanism of disease for SEDT.postprintThe 1st International Congress on Research of Rare and Orphan Diseases (RE(ACT) 2012), Basel, Switzerland, 29 February-2 March 2012. In Brochure of RE(ACT)® 2012, 2012, p. 11

Supporting women throughout the postpartum period: marital satisfaction and their emotional health

Conference Theme: Women's Health through the Life Cycle: the Asia PerspectivesPoster Presentation: no. 2postprintThe 10th Anniversary Symposium of the Centre of Research and Promotion of Women's Health, School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, 2-3 March 2011. In Symposium Abstract Book, 2011, p. 4

Clinical outcome of relapsing remitting multiple sclerosis among Hong Kong Chinese

PosterBACKGROUND: Many relapsing remitting multiple sclerosis (RRMS) patients develop irreversible progressive neurological disability. Reported clinical outcome varied. We aimed to study clinical outcome of Chinese RRMS patients. METHODS: Only RRMS patients …published_or_final_versio

Risk factors, clinical features and prognosis of perioperative stroke in adults

INTRODUCTION: Perioperative stroke (POS) is an uncommon but severe surgical complication. No widely accepted guidelines for risk prediction or management have been established. Its prevention depends on knowledge about the nature of this disease. METHODS: A total of 36 cases and equal number of controls in Hong Kong West Cluster hospitals were recruited over 43 months. Peri- and intra-operative features were compared and characteristics of POS were described. RESULTS: Atrial fibrillation, diabetes mellitus (DM), and history of stroke were identified as risk factors (P=0.017, 0.002, and 0.003, respectively). Prolonged aortic occlusion (P=0.018) and bypass (P=0.002) contributed in cardiac surgery. Only few BP parameters, but not consistently all, were significant; 78% POS were infarcts. Watershed infarction related to hypotension was uncommon. Beta-blocker use seemed to bare protective effect. Blood loss and haemoglobin levels did not correlate to POS. Three-month mortality rate was 36%. CONCLUSION: Optimal DM control and cardioversion before elective OT, perioperative anticoagulation in AF and old stroke patients, and beta-blockers may be preventive measures for POS. Role of hypotension in POS aetiology is debatable.published_or_final_versionThe 15th Medical Research Conference; Department of Medicine, The University of Hong Kong, Hong Kong, 16 January 2010. In Hong Kong Medical Journal, 2010, v. 16 suppl. 1, p. 13, abstract no.

Cerebral involvement in neuromyelitis optica spectrum disorders among Hong Kong Chinese

published_or_final_versionThe 16th Medical Resarch Conference (MRC), The University of Hong Kong, Hong Kong, China, 22 January 2011. In Hong Kong Medical Journal, 2011, v. 17, suppl. 1, p. 55, abstract no. 8

Floor transfer test for assessing people with chronic stroke

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Thymomatous myasthenia gravis

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder targeting skeletal muscle acetylcholine receptor. Thymoma is associated with MG in some patients, the majority of whom present with symptoms of MG before detection of underlying thymoma. This study aimed to study clinical and serological characteristics of Chinese thymomatous MG patients …published_or_final_versio

Severe liver failure due to influenza A infection in a hemodialysis patient

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Large-Scale Whole-Genome Sequencing Reveals the Genetic Architecture of Primary Membranoproliferative GN and C3 Glomerulopathy

BACKGROUND: Primary membranoproliferative GN, including complement 3 (C3) glomerulopathy, is a rare, untreatable kidney disease characterized by glomerular complement deposition. Complement gene mutations can cause familial C3 glomerulopathy, and studies have reported rare variants in complement genes in nonfamilial primary membranoproliferative GN. METHODS: We analyzed whole-genome sequence data from 165 primary membranoproliferative GN cases and 10,250 individuals without the condition (controls) as part of the National Institutes of Health Research BioResource–Rare Diseases Study. We examined copy number, rare, and common variants. RESULTS: Our analysis included 146 primary membranoproliferative GN cases and 6442 controls who were unrelated and of European ancestry. We observed no significant enrichment of rare variants in candidate genes (genes encoding components of the complement alternative pathway and other genes associated with the related disease atypical hemolytic uremic syndrome; 6.8% in cases versus 5.9% in controls) or exome-wide. However, a significant common variant locus was identified at 6p21.32 (rs35406322) (P=3.29×10−8; odds ratio [OR], 1.93; 95% confidence interval [95% CI], 1.53 to 2.44), overlapping the HLA locus. Imputation of HLA types mapped this signal to a haplotype incorporating DQA1*05:01, DQB1*02:01, and DRB1*03:01 (P=1.21×10−8; OR, 2.19; 95% CI, 1.66 to 2.89). This finding was replicated by analysis of HLA serotypes in 338 individuals with membranoproliferative GN and 15,614 individuals with nonimmune renal failure. CONCLUSIONS: We found that HLA type, but not rare complement gene variation, is associated with primary membranoproliferative GN. These findings challenge the paradigm of complement gene mutations typically causing primary membranoproliferative GN and implicate an underlying autoimmune mechanism in most cases