糖基化
外显子组测序
错义突变
智力残疾
生物
全球发育迟缓
小头畸形
遗传学
医学
生物信息学
基因
突变
表型
作者
Silvia Radenkovic,Diego Martinelli,Yuebo Zhang,Graeme Preston,Arianna Maiorana,Alessandra Terracciano,Maria Lisa Dentici,Elisa Pisaneschi,Antonio Novelli,Wasantha Ranatunga,Anna Ligezka,Bart Ghesquière,David R. Deyle,Tamas Kozicz,Filippo Pinto e Vairo,Peter Witters,Eva Morava
标识
DOI:10.1016/j.gim.2021.12.012
摘要
TRAPPC9 deficiency is an autosomal recessive disorder mainly associated with intellectual disability (ID), microcephaly, and obesity. Previously, TRAPPC9 deficiency has not been associated with biochemical abnormalities.Exome sequencing was performed in 3 individuals with ID and dysmorphic features. N-Glycosylation analyses were performed in the patients' blood samples to test for possible congenital disorder of glycosylation (CDG). TRAPPC9 gene, TRAPPC9 protein expression, and N-glycosylation markers were assessed in patient fibroblasts. Complementation with wild-type TRAPPC9 and immunofluorescence studies to assess TRAPPC9 expression and localization were performed. The metabolic consequences of TRAPPC9 deficiency were evaluated using tracer metabolomics.All 3 patients carried biallelic missense variants in TRAPPC9 and presented with an N-glycosylation defect in blood, consistent with CDG type I. Extensive investigations in patient fibroblasts corroborated TRAPPC9 deficiency and an N-glycosylation defect. Tracer metabolomics revealed global metabolic changes with several affected glycosylation-related metabolites.We identified 3 TRAPPC9 deficient patients presenting with ID, dysmorphic features, and abnormal glycosylation. On the basis of our findings, we propose that TRAPPC9 deficiency could lead to a CDG (TRAPPC9-CDG). The finding of abnormal glycosylation in these patients is highly relevant for diagnosis, further elucidation of the pathophysiology, and management of the disease.
科研通智能强力驱动
Strongly Powered by AbleSci AI