No abstract

Background Congenital adrenal hyperplasia (CAH) screening is facing great challenges because of a high false-positive rate and a low positive predictive value (PPV). We established and optimized 17-hydroxyprogesterone (17-OHP) cut-off values for CAH neonatal screening using a genetic screening processor (GSP) according to gestational age (GA), birth weight (BW) and age at sampling. Methods The 17-OHP concentrations in dried blood spots were measured by time-resolved immunofluorescence and were grouped in terms of GA, BW and age at sampling for 48,592 newborns. The 99.5th percentile was used to set an initial cut-off value as a reference. Results Significant differences in 17-OHP concentrations were observed among newborns with different GAs and BWs. A significant difference was observed among different sampling age groups. Finally, we defined new multitier cut-off concentrations based on GA and age at sampling. Application of the new cut-off values resulted in a 30% reduction of the positive rate and a 40% increase of the PPV. Conclusions GA, BW and sampling age time influenced the concentrations of 17-OHP. The efficiency of congenital adrenal hyperplasia screening can be substantially improved by adjusting the multitier cut-off value according to GA and age at sampling.

No abstract

GM1 gangliosidosis is a rare lysosomal storage disease caused by a deficiency of β-galactosidase due to mutations in the GLB1 gene. We established a C57BL/6 mouse model with Glb1G455R mutation using CRISPR/Cas9 genome editing. The β-galactosidase enzyme activity of Glb1G455R mice measured by fluorometric assay was negligible throughout the whole body. Mutant mice displayed no marked phenotype at eight weeks. After 16 weeks, GM1 ganglioside accumulation in the brain of mutant mice was observed by immunohistochemical staining. Meanwhile, a declining performance in behavioral tests was observed among mutant mice from 16 to 32 weeks. As the disease progressed, the neurological symptoms of mutant mice worsened, and they then succumbed to the disease by 47 weeks of age. We also observed microglia activation and proliferation in the cerebral cortex of mutant mice at 16 and 32 weeks. In these activated microglia, the level of autophagy regulator LC3 was up-regulated but the mRNA level of LC3 was normal. In conclusion, we developed a novel murine model that mimicked the chronic phenotype of human GM1. This Glb1G455R murine model is a practical in vivo model for studying the pathogenesis of GM1 gangliosidosis and exploring potential therapies.

No abstract