Pujol Gimenez, JonaiJonaiPujol GimenezMirzaa, GhaydaGhaydaMirzaaBlue, Elizabeth EElizabeth EBlueAlbano, GiuseppeGiuseppeAlbanoMiller, Danny EDanny EMillerAllworth, AimeeAimeeAllworthBennett, James TJames TBennettByers, Peter HPeter HByersChanprasert, SirisakSirisakChanprasertChen, JinghengJinghengChenDoherty, DanielDanielDohertyFolta, Andrew BAndrew BFoltaGillentine, Madelyn AMadelyn AGillentineGlass, IanIanGlassHing, AnneAnneHingHorike-Pyne, MarthaMarthaHorike-PyneLeppig, Kathleen AKathleen ALeppigParhin, AzmaAzmaParhinRanchalis, JaneJaneRanchalisRaskind, Wendy HWendy HRaskindRosenthal, Elisabeth AElisabeth ARosenthalSchwarze, UlrikeUlrikeSchwarzeSheppeard, SamSamSheppeardStrohbehn, SamuelSamuelStrohbehnSybert, Virginia PVirginia PSybertTimms, AndrewAndrewTimmsWener, MarkMarkWenerBamshad, Michael JMichael JBamshadHisama, Fuki MFuki MHisamaJarvik, Gail PGail PJarvikDipple, Katrina MKatrina MDippleHediger, MatthiasMatthiasHediger0000-0003-1946-027XStergachis, Andrew BAndrew BStergachis2024-10-252024-10-252023-06https://boris-portal.unibe.ch/handle/20.500.12422/167208SLC1A4 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.en600 - Technology::610 - Medicine & healtharticle10.48350/1826613719441610.1002/acn3.51786