PMID- 33734437
OWN - NLM
STAT- MEDLINE
DCOM- 20220117
LR  - 20221005
IS  - 1573-2665 (Electronic)
IS  - 0141-8955 (Print)
IS  - 0141-8955 (Linking)
VI  - 44
IP  - 4
DP  - 2021 Jul
TI  - ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and 
      expanded phenotypes.
PG  - 1001-1012
LID - 10.1002/jimd.12378 [doi]
AB  - 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.
CI  - (c) 2021 SSIEM.
FAU - Alsharhan, Hind
AU  - Alsharhan H
AUID- ORCID: 0000-0002-6433-0311
AD  - Division of Human Genetics, Department of Pediatrics, The Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
AD  - Department of Pathology and Laboratory Medicine, The Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
AD  - Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, 
      Kuwait.
FAU - He, Miao
AU  - He M
AD  - Department of Pathology and Laboratory Medicine, The Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
FAU - Edmondson, Andrew C
AU  - Edmondson AC
AD  - Division of Human Genetics, Department of Pediatrics, The Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
FAU - Daniel, Earnest J P
AU  - Daniel EJP
AD  - Department of Pathology and Laboratory Medicine, The Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
FAU - Chen, Jie
AU  - Chen J
AD  - Department of Pathology and Laboratory Medicine, The Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
FAU - Donald, Tyhiesia
AU  - Donald T
AD  - Pediatrics Ward, Grenada General Hospital, St. George's, Grenada.
AD  - Clinical Teaching Unit, St. George's University, St. George's, Grenada.
FAU - Bakhtiari, Somayeh
AU  - Bakhtiari S
AD  - Pediatric Movement Disorders Program, Division of Pediatric Neurology, Barrow 
      Neurological Institute, Phoenix Children's Hospital, Phoenix, Arizona, USA.
AD  - Departments of Child Health, Neurology, Cellular & Molecular Medicine and Program 
      in Genetics, University of Arizona College of Medicine, Phoenix, Arizona, USA.
FAU - Amor, David J
AU  - Amor DJ
AD  - Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, and 
      Department of Pediatrics, University of Melbourne, Melbourne, Australia.
FAU - Jones, Elizabeth A
AU  - Jones EA
AD  - Manchester Centre for Genomic Medicine, Saint Mary's Hospital, Manchester 
      University NHS Foundation Trust, Manchester, UK.
AD  - Division of Evolution and Genomic Sciences, School of Biological Sciences, 
      Faculty of Biology, Medicine and Health, University of Manchester, Manchester 
      Academic Health Science Centre, Manchester, UK.
FAU - Vassallo, Grace
AU  - Vassallo G
AD  - Department of Pediatric Neurology, Royal Manchester Children's Hospital, 
      Manchester University Foundation Trust, Manchester, UK.
FAU - Vincent, Marie
AU  - Vincent M
AD  - Service de genetique medicale, CHU de Nantes, Nantes, France.
FAU - Cogne, Benjamin
AU  - Cogne B
AD  - Service de genetique medicale, CHU de Nantes, Nantes, France.
FAU - Deb, Wallid
AU  - Deb W
AD  - Service de genetique medicale, CHU de Nantes, Nantes, France.
FAU - Werners, Arend H
AU  - Werners AH
AD  - Department of Anatomy, Physiology and Pharmacology, St. George University School 
      of Veterinary Medicine, St. George's, Grenada.
FAU - Jin, Sheng C
AU  - Jin SC
AD  - Department of Genetics and Pediatrics, Washington University, St. Louis, 
      Missouri, USA.
FAU - Bilguvar, Kaya
AU  - Bilguvar K
AD  - Department of Genetics, Yale Center for Genome Analysis, Yale School of Medicine, 
      New Haven, Connecticut, USA.
FAU - Christodoulou, John
AU  - Christodoulou J
AD  - Brain and Mitochondrial Research Group, Murdoch Children's Research Institute, 
      Royal Children's Hospital, Melbourne, and Department of Pediatrics, University of 
      Melbourne, Melbourne, Australia.
AD  - Discipline of Child & Adolescent Health, Sydney Medical School, University of 
      Sydney, Sydney, Australia.
FAU - Webster, Richard I
AU  - Webster RI
AD  - Institute for Neuroscience and Muscle Research, The Children's Hospital at 
      Westmead, Sydney, New South Wales, Australia.
FAU - Yearwood, Katherine R
AU  - Yearwood KR
AD  - St. George's University, University Health Services, St. George's, Grenada.
FAU - Ng, Bobby G
AU  - Ng BG
AD  - Human Genetics Program, Sanford Children's Health Research Center, Sanford 
      Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.
FAU - Freeze, Hudson H
AU  - Freeze HH
AD  - Human Genetics Program, Sanford Children's Health Research Center, Sanford 
      Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.
FAU - Kruer, Michael C
AU  - Kruer MC
AD  - Pediatric Movement Disorders Program, Division of Pediatric Neurology, Barrow 
      Neurological Institute, Phoenix Children's Hospital, Phoenix, Arizona, USA.
AD  - Departments of Child Health, Neurology, Cellular & Molecular Medicine and Program 
      in Genetics, University of Arizona College of Medicine, Phoenix, Arizona, USA.
FAU - Li, Dong
AU  - Li D
AD  - Division of Human Genetics, Department of Pediatrics, The Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
FAU - Raymond, Kimiyo M
AU  - Raymond KM
AD  - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, 
      Minnesota, USA.
FAU - Bhoj, Elizabeth J
AU  - Bhoj EJ
AD  - Division of Human Genetics, Department of Pediatrics, The Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
FAU - Sobering, Andrew K
AU  - Sobering AK
AD  - Department of Biochemistry, St. George's University School of Medicine, St. 
      George's, Grenada.
AD  - Windward Islands Research and Education Foundation, True Blue, St. George's, 
      Grenada.
LA  - eng
GR  - T32 GM008638/GM/NIGMS NIH HHS/United States
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
GR  - R00 HL143036/HL/NHLBI NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
GR  - UM1 HG006504/HG/NHGRI NIH HHS/United States
GR  - U54 NS115198/NS/NINDS NIH HHS/United States
GR  - R01 DK099551/DK/NIDDK NIH HHS/United States
GR  - U24 HG008956/HG/NHGRI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210326
PL  - United States
TA  - J Inherit Metab Dis
JT  - Journal of inherited metabolic disease
JID - 7910918
RN  - 0 (Transferrin)
RN  - EC 2.4.1.- (ALG13 protein, human)
RN  - EC 2.4.1.- (N-Acetylglucosaminyltransferases)
SB  - IM
MH  - Congenital Disorders of Glycosylation/*genetics/physiopathology
MH  - Female
MH  - Genetic Variation
MH  - Glycosylation
MH  - Humans
MH  - Intellectual Disability/genetics/*physiopathology
MH  - Male
MH  - N-Acetylglucosaminyltransferases/*genetics
MH  - Phenotype
MH  - Transferrin/metabolism
PMC - PMC8720508
MID - NIHMS1763418
OTO - NOTNLM
OT  - N-glycans
OT  - carbohydrate deficient transferrin
OT  - congenital disorders of glycosylation
OT  - epilepsy
OT  - exome sequencing
OT  - mass spectrometry
COIS- CONFLICT OF INTEREST H. H. F. is a consultant for Cerecor, Inc. The other authors 
      declare that they have no conflicts of interest.
EDAT- 2021/03/19 06:00
MHDA- 2022/01/18 06:00
PMCR- 2022/01/02
CRDT- 2021/03/18 12:50
PHST- 2021/03/15 00:00 [revised]
PHST- 2020/10/22 00:00 [received]
PHST- 2021/03/17 00:00 [accepted]
PHST- 2021/03/19 06:00 [pubmed]
PHST- 2022/01/18 06:00 [medline]
PHST- 2021/03/18 12:50 [entrez]
PHST- 2022/01/02 00:00 [pmc-release]
AID - 10.1002/jimd.12378 [doi]
PST - ppublish
SO  - J Inherit Metab Dis. 2021 Jul;44(4):1001-1012. doi: 10.1002/jimd.12378. Epub 2021 
      Mar 26.