High-throughput mutational analysis of TOR1A in primary dystonia

<p>Abstract</p> <p>Background</p> <p>Although the c.904_906delGAG mutation in Exon 5 of <it>TOR1A </it>typically manifests as early-onset generalized dystonia, DYT1 dystonia is genetically and clinically heterogeneous. Recently, another Exon 5 mutation (c.863G>A) has been associated with early-onset generalized dystonia and some ΔGAG mutation carriers present with late-onset focal dystonia. The aim of this study was to identify <it>TOR1A </it>Exon 5 mutations in a large cohort of subjects with mainly non-generalized primary dystonia.</p> <p>Methods</p> <p>High resolution melting (HRM) was used to examine the entire <it>TOR1A </it>Exon 5 coding sequence in 1014 subjects with primary dystonia (422 spasmodic dysphonia, 285 cervical dystonia, 67 blepharospasm, 41 writer's cramp, 16 oromandibular dystonia, 38 other primary focal dystonia, 112 segmental dystonia, 16 multifocal dystonia, and 17 generalized dystonia) and 250 controls (150 neurologically normal and 100 with other movement disorders). Diagnostic sensitivity and specificity were evaluated in an additional 8 subjects with known ΔGAG DYT1 dystonia and 88 subjects with ΔGAG-negative dystonia.</p> <p>Results</p> <p>HRM of <it>TOR1A </it>Exon 5 showed high (100%) diagnostic sensitivity and specificity. HRM was rapid and economical. HRM reliably differentiated the <it>TOR1A </it>ΔGAG and c.863G>A mutations. Melting curves were normal in 250/250 controls and 1012/1014 subjects with primary dystonia. The two subjects with shifted melting curves were found to harbor the classic ΔGAG deletion: 1) a non-Jewish Caucasian female with childhood-onset multifocal dystonia and 2) an Ashkenazi Jewish female with adolescent-onset spasmodic dysphonia.</p> <p>Conclusion</p> <p>First, HRM is an inexpensive, diagnostically sensitive and specific, high-throughput method for mutation discovery. Second, Exon 5 mutations in <it>TOR1A </it>are rarely associated with non-generalized primary dystonia.</p

Retro-Commissioning – Effective Energy Conservation Initiatives in Existing Buildings

Abstract Hong Kong is a densely populated metropolitan city crowded with more than 7 million people. of the 42,000 buildings in Hong Kong, more than half (55%) of Hong Kong’s total annual energy end-use is in the form of electricity consumption and buildings take up about 90% of our total electricity consumption. Thus, energy saving in buildings is a key factor of addressing climate change and associated environmental issues of Hong Kong. In January 2017, the Environment Bureau of Hong Kong Special Administration Region Government (HKSARG) published “Hong Kong’s Climate Action Plan 2030+” which set target to reduce our carbon intensity by 65-70% by 2030 compared with the 2005 level. With this ambitious vision, the whole community have to further endeavour to achieve energy conservation with concrete supporting measures. Electrical and Mechanical Services Department (EMSD) of HKSARG is actively pursuing the cost-effective program of “Retro-commissioning (RCx)”, new energy saving initiative, to further encourage energy conservation works in existing buildings. RCx is a cost-effective and systematic process to periodically check the energy efficiency performance of existing building. EMSD has carried out numbers of pilot projects on both government and private buildings with Hong Kong Green Building Council (HKGBC); launched the “Technical Guidelines on Retro-commissioning [TG(RCx)]”; led and co-organized with different stakeholders on showcasing the government-industry collaboration and promoting effort of RCx training for the industry. The paper will introduce the framework and technical approach of TG(RCx), share the latest development and implementation programme of RCx in Hong Kong.</jats:p