Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy

Undiagnosed Phenylketonuria Can Exist Everywhere: Results From an International Survey

peer reviewedMany countries do not have a newborn screening (NBS) program, and immigrants from such countries are at risk for late diagnosis of phenylketonuria (PKU). In this international survey, 52 of 259 patients (20%) with late diagnosed PKU were immigrants, and 145 of the 259 (55%) were born before NBS or in a location without NBS. © 2021 The Author

Clinical application of next-generation sequencing for Mendelian diseases

10.1186/s40246-015-0031-5Human genomics91

Using high performance computing to create and freely distribute the South Asian genomic database, necessary for precision medicine in this population

10.14529/jsfi170201Supercomputing Frontiers and Innovations424-De

FGMOS-based NMC-RC frequency compensation differential amplifier for low power low voltage applications

This paper presents how to add flexibility to reduce the overall power consumption in a CMOS operational amplifier by replacing few MOS transistors with floating gate MOSFET (FGMOS). The disadvantages of doing this are also discussed. The performance of the proposed circuit using unity gain bandwidth (GBW) and slew rate (SR) as figure of merit is presented. The Nested Miller compensation (NMC) is used and the pole is positioned far away from first pole in frequency spectrum for frequency compensation resulting. The zero from RC network is also matched to the non-dominant pole at the left-side of the Nyquist plot of the loop to increase stability and control the bandwidth operation. The circuit operates with a voltage supply of 0.5V and has 26.7uW power consumption

Next-generation sequencing using a pre-designed gene panel for the molecular diagnosis of congenital disorders in pediatric patients

10.1186/s40246-015-0055-xHuman genomics93

DISSEMINATED BACILLUS-CALMETTE-GU蒖IN INFECTIONS AND PRIMARY IMMUNODEFICIENCY DISORDERS IN SINGAPORE: A SINGLE CENTER 15-YEAR RETROSPECTIVE REVIEW

10.1016/j.ijid.2020.05.117International Journal of Infectious Diseases97117-12