@article{aff6472add6347f78ff1d22113b3c5c0,
title = "ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes",
abstract = "Pathogenic variants in ALG13 (ALG13 UDP-N-acetylglucosaminyltransferase subunit) cause an X-linked congenital disorder of glycosylation (ALG13-CDG) where individuals have variable clinical phenotypes that include developmental delay, intellectual disability, infantile spasms, and epileptic encephalopathy. Girls with a recurrent de novo c.3013C>T; p.(Asn107Ser) variant have normal transferrin glycosylation. Using a highly sensitive, semi-quantitative flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) N-glycan assay, we report subtle abnormalities in N-glycans that normally account for <0.3% of the total plasma glycans that may increase up to 0.5% in females with the p.(Asn107Ser) variant. Among our 11 unrelated ALG13-CDG individuals, one male had abnormal serum transferrin glycosylation. We describe seven previously unreported subjects including three novel variants in ALG13 and report a milder neurodevelopmental course. We also summarize the molecular, biochemical, and clinical data for the 53 previously reported ALG13-CDG individuals. We provide evidence that ALG13 pathogenic variants may mildly alter N-linked protein glycosylation in both female and male subjects, but the underlying mechanism remains unclear.",
keywords = "N-glycans, carbohydrate deficient transferrin, congenital disorders of glycosylation, epilepsy, exome sequencing, mass spectrometry",
author = "Hind Alsharhan and Miao He and Edmondson, {Andrew C.} and Daniel, {Earnest J.P.} and Jie Chen and Tyhiesia Donald and Somayeh Bakhtiari and Amor, {David J.} and Jones, {Elizabeth A.} and Grace Vassallo and Marie Vincent and Benjamin Cogn{\'e} and Wallid Deb and Werners, {Arend H.} and Jin, {Sheng C.} and Kaya Bilguvar and John Christodoulou and Webster, {Richard I.} and Yearwood, {Katherine R.} and Ng, {Bobby G.} and Freeze, {Hudson H.} and Kruer, {Michael C.} and Dong Li and Raymond, {Kimiyo M.} and Bhoj, {Elizabeth J.} and Sobering, {Andrew K.}",
note = "Funding Information: We thank the patients and their families for participating in this study. This study makes use of data generated by the DECIPHER community. A full list of centers who contributed to the generation of the data is available from https://decipher.sanger.ac.uk and via email from decipher@sanger.ac.uk. Funding for the project was provided by Wellcome. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between Wellcome and the Department of Health, and the Wellcome Sanger Institute (grant number WT098051). The views expressed in this publication are those of the author(s) and not necessarily those of Wellcome or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12 granted by the Republic of Ireland REC). We acknowledge the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network. The Yale Center for Mendelian Genomics (UM1HG006504) is funded by the National Human Genome Research Institute. The GSP Coordinating Center (U24 HG008956) contributed to cross-program scientific initiatives and provided logistical and general study coordination. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The research conducted at the Murdoch Children's Research Institute was supported by the State Government of Victoria's Operational Infrastructure Support Program. Finally, we thank the members of the Epi4K Consortium. This work was supported by National Institutes of Health grants U54 NS115198 (A. C. E., M. H., and H. H. F.), T32 GM008638 (A. C. E.), and R01DK99551 (H. H. F.). Funding Information: We thank the patients and their families for participating in this study. This study makes use of data generated by the DECIPHER community. A full list of centers who contributed to the generation of the data is available from https://decipher.sanger.ac.uk and via email from decipher@sanger.ac.uk . Funding for the project was provided by Wellcome. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF‐1009‐003), a parallel funding partnership between Wellcome and the Department of Health, and the Wellcome Sanger Institute (grant number WT098051). The views expressed in this publication are those of the author(s) and not necessarily those of Wellcome or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12 granted by the Republic of Ireland REC). We acknowledge the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network. The Yale Center for Mendelian Genomics (UM1HG006504) is funded by the National Human Genome Research Institute. The GSP Coordinating Center (U24 HG008956) contributed to cross‐program scientific initiatives and provided logistical and general study coordination. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The research conducted at the Murdoch Children's Research Institute was supported by the State Government of Victoria's Operational Infrastructure Support Program. Finally, we thank the members of the Epi4K Consortium. This work was supported by National Institutes of Health grants U54 NS115198 (A. C. E., M. H., and H. H. F.), T32 GM008638 (A. C. E.), and R01DK99551 (H. H. F.). Funding Information: National Institutes of Health, Grant/Award Numbers: R01DK99551, T32 GM008638, U54 NS115198; State Government of Victoria; National Human Genome Research Institute; National Institute for Health Research; Wellcome Sanger Institute, Grant/Award Number: WT098051; Department of Health; Health Innovation Challenge Fund, Grant/Award Number: HICF‐1009‐003; Wellcome Funding information Publisher Copyright: {\textcopyright} 2021 SSIEM.",
year = "2021",
month = jul,
doi = "10.1002/jimd.12378",
language = "English (US)",
volume = "44",
pages = "1001--1012",
journal = "Journal of Inherited Metabolic Disease",
issn = "0141-8955",
publisher = "Springer Netherlands",
number = "4",
}