%0 Journal Article
%T ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes.
%A Alsharhan H
%A He M
%A Edmondson AC
%A Daniel EJP
%A Chen J
%A Donald T
%A Bakhtiari S
%A Amor DJ
%A Jones EA
%A Vassallo G
%A Vincent M
%A Cogné B
%A Deb W
%A Werners AH
%A Jin SC
%A Bilguvar K
%A Christodoulou J
%A Webster RI
%A Yearwood KR
%A Ng BG
%A Freeze HH
%A Kruer MC
%A Li D
%A Raymond KM
%A Bhoj EJ
%A Sobering AK
%J J Inherit Metab Dis
%V 44
%N 4
%D 07 2021
%M 33734437
%F 4.75
%R 10.1002/jimd.12378
%X 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.