Predominant and novel de novo variants in 29 individuals withALG13deficiency: Clinical description, biomarker status, biochemical analysis, and treatment suggestions
Bobby G Ng, Erik A Eklund, Sergey A Shiryaev, Yin Y Dong, Mary-Alice Abbott, Carla Asteggiano, Michael J Bamshad, Eileen Barr, Jonathan A Bernstein, Shabeed Chelakkadan, John Christodoulou, Wendy K Chung, Michael A Ciliberto, Janice Cousin, Fiona Gardiner, Suman Ghosh, William D Graf, Stephanie Grunewald, Katherine Hammond, Natalie S Hauser Show all
JOURNAL OF INHERITED METABOLIC DISEASE | WILEY | Published : 2020
Asparagine-linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X-linked uridine diphosphate (UDP)-N-acetylglucosaminyltransferase required for the synthesis of lipid linked oligosaccharide precursor and proper N-linked glycosylation. De novo variants in ALG13 underlie a form of early infantile epileptic encephalopathy known as EIEE36, but given its essential role in glycosylation, it is also considered a congenital disorder of glycosylation (CDG), ALG13-CDG. Twenty-four previously reported ALG13-CDG cases had de novo variants, but surprisingly, unlike most forms of CDG, ALG13-CDG did not show the anticipated glycosylation defects, typically detected by altered t..View full abstract
Awarded by Rocket Fund, National Institutes of Health (NIH)
Awarded by NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH
Awarded by University of Washington Center for Mendelian Genomics through NHLBI
We would like to thank all the families for their continued support and for providing valuable biological specimens. We thank Dr Neta Dean for the ALG13 deficient yeast strain and expression plasmids. We also thank Mrs Krista Williams for her supporting the ALG13 family Facebook support group. This work was supported in part by the Intramural Research Program of the National Human Genome Research Institute. We thank Jamie Smolin for technical help. This work was also supported by the Rocket Fund, National Institutes of Health (NIH) grants R01DK099551 (to H. H. F) and partial funding from U54 NS115198. Regional funding, Region Skane, Sweden (to E. A. E). JPB Foundation (to W. K. C), SFARI (to W. K. C.). Research reported in this manuscript was supported by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director under Award Number U01HG007708 and U01HG010218. The University of Washington Center for Mendelian Genomics through NHGRI and NHLBI grants UM1 HG006493 and U24 HG008956. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. I. E. S. has served on scientific advisory boards for UCB, Eisai, GlaxoSmithKline, BioMarin, Nutricia, Rogcon and Xenon Pharmaceuticals; has received speaker honoraria from GlaxoSmithKline, UCB, BioMarin, Biocodex and Eisai; has received funding for travel from UCB, Biocodex, GlaxoSmithKline, Biomarin and Eisai; has served as an investigator for Zogenix, Zynerba, Ultragenyx, GW Pharma, UCB, Eisai, Anavex Life Sciences and Marinus; and has consulted for Zynerba Pharmaceuticals, Atheneum Partners, Ovid Therapeutics and UCB. She receives/has received research support from the National Health and Medical Research Council of Australia, Health Research Council of New Zealand, CURE, Australian Epilepsy Research Fund, March of Dimes and NIH/NINDS.