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.

中文翻译：

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ALG13 X 连锁智力障碍：新变体、糖基化分析和扩展表型

ALG13 ( ALG13 UDP-N-乙酰氨基葡糖转移酶亚基)中的致病变异) 导致 X 连锁先天性糖基化障碍 (ALG13-CDG)，其中个体具有不同的临床表型，包括发育迟缓、智力残疾、婴儿痉挛和癫痫性脑病。复发性从头 c.3013C>T 的女孩；p.(Asn107Ser) 变体具有正常的转铁蛋白糖基化。使用高度灵敏的半定量流动注射-电喷雾电离-四极杆飞行时间质谱 (ESI-QTOF/MS) N-聚糖测定，我们报告了 N-聚糖的细微异常，通常占小于 0.3%在具有 p.(Asn107Ser) 变体的女性中，总血浆聚糖可能增加高达 0.5%。在我们的 11 名不相关的 ALG13-CDG 个体中，一名男性的血清转铁蛋白糖基化异常。我们描述了七个以前未报告的主题，包括三个新的变体ALG13并报告​​了较温和的神经发育过程。我们还总结了 53 名先前报道的 ALG13-CDG 个体的分子、生化和临床数据。我们提供的证据表明，ALG13致病变异可能会轻微改变女性和男性受试者的 N-连接蛋白糖基化，但潜在的机制仍不清楚。