Centro de Diagnóstico de Enfermedades Moleculares, Center of Molecular Biology Severo Ochoa (CBMSO), Autonomous University of Madrid, CIBERER, IdiPAZ, Madrid, Spain.
Sant Joan de Déu Research Institute, CIBERER, Barcelona, Spain.
Clin Genet. 2022 Jul;102(1):40-55. doi: 10.1111/cge.14138. Epub 2022 Apr 15.
Glucose transporter 1 deficiency syndrome (GLUT1DS) is a neurometabolic disorder caused by haploinsufficiency of the GLUT1 glucose transporter (encoded by SLC2A1) leading to defective glucose transport across the blood-brain barrier. This work describes the genetic analysis of 56 patients with clinical or biochemical GLUT1DS hallmarks. 55.4% of these patients had a pathogenic variant of SLC2A1, and 23.2% had a variant in one of 13 different genes. No pathogenic variant was identified for the remaining patients. Expression analysis of SLC2A1 indicated a reduction in SLC2A1 mRNA in patients with pathogenic variants of this gene, as well as in one patient with a pathogenic variant in SLC9A6, and in three for whom no candidate variant was identified. Thus, the clinical and biochemical hallmarks generally associated with GLUT1DS may be caused by defects in genes other than SLC2A1.
葡萄糖转运蛋白 1 缺乏综合征（GLUT1DS）是一种神经代谢疾病，由 GLUT1 葡萄糖转运蛋白（由 SLC2A1 编码）的单倍体不足引起，导致葡萄糖穿过血脑屏障的转运缺陷。本研究描述了 56 名具有临床或生化 GLUT1DS 特征的患者的基因分析。这些患者中有 55.4%携带 SLC2A1 的致病性变异，23.2%携带 13 个不同基因中的一个变异。其余患者未发现致病性变异。SLC2A1 的表达分析表明，该基因的致病性变异患者以及 SLC9A6 致病性变异患者和三个未发现候选变异患者的 SLC2A1 mRNA 减少。因此，通常与 GLUT1DS 相关的临床和生化特征可能是由 SLC2A1 以外的基因缺陷引起的。
