Dominant-negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome.
Dominant-negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome.
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DOI：
10.1002/acn3.51786
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发表时间：
2023-06
影响因子：
5.3
通讯作者：
Stergachis, Andrew B.
中科院分区：
文献类型：
--
作者：
Pujol-Gimenez, Jonai;Mirzaa, Ghayda;Blue, Elizabeth E.;Albano, Giuseppe;Miller, Danny E.;Allworth, Aimee;Bennett, James T.;Byers, Peter H.;Chanprasert, Sirisak;Chen, Jingheng;Doherty, Daniel;Folta, Andrew B.;Gillentine, Madelyn A.;Glass, Ian;Hing, Anne;Horike-Pyne, Martha;Leppig, Kathleen A.;Parhin, Azma;Ranchalis, Jane;Raskind, Wendy H.;Rosenthal, Elisabeth A.;Schwarze, Ulrike;Sheppeard, Sam;Strohbehn, Samuel;Sybert, Virginia P.;Timms, Andrew;Wener, Mark;Bamshad, Michael J.;Hisama, Fuki M.;Jarvik, Gail P.;Dipple, Katrina M.;Hediger, Matthias A.;Stergachis, Andrew B.
SLC 1A 4是将L-丝氨酸从星形胶质细胞穿梭到神经元所必需的三聚体中性氨基酸转运蛋白。已知具有SLC 1A 4双等位基因变体的个体患有痉挛性四肢瘫痪、胼胝体稀疏和进行性小头畸形（SPATCCM）综合征，但具有杂合变体的个体被认为没有疾病。我们确定了一名8岁的患者，患有全面发育迟缓、痉挛、癫痫和小头畸形，在SLC 1A 4（L86_M88dup）中有一个新生杂合的三个氨基酸重复。我们证明L86_M88dup导致SLC 1A 4的显性负性N-糖基化缺陷，这反过来降低了SLC 1A 4的质膜定位和SLC 1A 4对L-丝氨酸的转运速率。
SLC1A4 is a trimeric neutral amino acid transporter essential for shuttling L‐serine from astrocytes into neurons. Individuals with biallelic variants in SLC1A4 are known to have spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM) syndrome, but individuals with heterozygous variants are not thought to have disease. We identify an 8‐year‐old patient with global developmental delay, spasticity, epilepsy, and microcephaly who has a de novo heterozygous three amino acid duplication in SLC1A4 (L86_M88dup). We demonstrate that L86_M88dup causes a dominant‐negative N‐glycosylation defect of SLC1A4, which in turn reduces the plasma membrane localization of SLC1A4 and the transport rate of SLC1A4 for L‐serine.
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影响因子：
6
作者：
Stehantsev P;Stetsenko A;Nemchinova M;Aduri NG;Marrink SJ;Gati C;Guskov A
通讯作者：
Guskov A
影响因子：
1.9
作者：
Sarigecili, Esra;Bulut, Fatma Derya;Anlas, Ozlem
通讯作者：
Anlas, Ozlem
影响因子：
5.4
作者：
Marin, M;Lavillette, D;Kabat, D
通讯作者：
Kabat, D
影响因子：
3.5
作者：
Heimer, G.;Marek-Yagel, D.;Ben Zeev, B.
通讯作者：
Ben Zeev, B.
影响因子：
1.9
作者：
Sedlackova, Lucie;Lassuthova, Petra;Seeman, Pavel
通讯作者：
Seeman, Pavel