A New Glycogen Storage Disease Caused by a Dominant PYGM Mutation.

OBJECTIVE: Glycogen storage diseases (GSDs) are severe human disorders resulting from abnormal glucose metabolism, and all previously described GSDs segregate as autosomal recessive or X-linked traits. In this study, we aimed to molecularly characterize the first family with a dominant GSD. METHODS: We describe a dominant GSD family with 13 affected members presenting with adult-onset muscle weakness, and we provide clinical, metabolic, histological, and ultrastructural data. We performed exome sequencing to uncover the causative gene, and functional experiments in the cell model and on recombinant proteins to investigate the pathogenic effect of the identified mutation. RESULTS: We identified a heterozygous missense mutation in PYGM segregating with the disease in the family. PYGM codes for myophosphorylase, the enzyme catalyzing the initial step of glycogen breakdown. Enzymatic tests revealed that the PYGM mutation impairs the AMP-independent myophosphorylase activity, whereas the AMP-dependent activity was preserved. Further functional investigations demonstrated an altered conformation and aggregation of mutant myophosphorylase, and the concurrent accumulation of the intermediate filament desmin in the myofibers of the patients. INTERPRETATION: Overall, this study describes the first example of a dominant glycogen storage disease in humans, and elucidates the underlying pathomechanisms by deciphering the sequence of events from the PYGM mutation to the accumulation of glycogen in the muscle fibers. ANN NEUROL 2020;88:274-282.

Spatiotemporal analysis of ground and satellite-based aerosol for air quality assessment in the Southeast Asia region.

Satellite observations for regional air quality assessment rely on comprehensive spatial coverage, and daily monitoring with reliable, cloud-free data quality. We investigated spatiotemporal variation and data quality of two global satellite Aerosol Optical Depth (AOD) products derived from MODIS and VIIRS imagery. AOD is considered an essential atmospheric parameter strongly related to ground Particulate Matter (PM) in Southeast Asia (SEA). We analyze seasonal variation, urban/rural area influence, and biomass burning effects on atmospheric pollution. Validation indicated a strong relationship between AERONET ground AOD and both MODIS AOD (R2 = 0.81) and VIIRS AOD (R2 = 0.68). The monthly variation of satellite AOD and AERONET AOD reflects two seasonal trends of air quality separately for mainland countries including Myanmar, Laos, Cambodia, Thailand, Vietnam, and Taiwan, Hong Kong, and for maritime countries consisting of Indonesia, Philippines, Malaysia, Brunei, Singapore, and Timor Leste. The mainland SEA has a pattern of monthly AOD variation in which AODs peak in March/April, decreasing during wet season from May-September, and increasing to the second peak in October. However, in maritime SEA, AOD concentration peaks in October. The three countries with the highest annual satellite AODs are Singapore, Hong Kong, and Vietnam. High urban population proportions in Singapore (40.7%) and Hong Kong (21.6%) were associated with high AOD concentrations as expected. AOD values in SEA urban areas were a factor of 1.4 higher than in rural areas, with respective averages of 0.477 and 0.336. The AOD values varied proportionately to the frequency of biomass burning in which both active fires and AOD peak in March/April and September/October. Peak AOD in September/October in some countries could be related to pollutant transport of Indonesia forest fires. This study analyzed satellite aerosol product quality in relation to AERONET in SEA countries and highlighted framework of air quality assessment over a large, complicated region.