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