biostudies-literatureUnknown39(6)Hortnagel KVesicular protein sorting-associated proteins (VPS, including VPS11) are indispensable in the endocytic network, in particular the endosome-lysosome biogenesis. Exome sequencing revealed the homozygous variant p.Leu387_ Gly395del in the VPS11 gene in two siblings. On immunoblotting, the mutant VPS11 protein showed a distinctly reduced immunostaining intensity. The children presented with primary and severe developmental delay associated with myoclonic seizures, spastic tetraplegia, trunk and neck hypotonia, blindness, hearing loss, and microcephaly. Neuro-imaging showed severe hypomyelination affecting cerebral and cerebellar white matter and corpus callosum, in the absence of a peripheral neuropathy. Electron microscopy of a skin biopsy revealed clusters of membranous cytoplasmic bodies iJournal of inherited metabolic disease849-857https://www.ebi.ac.uk/biostudies/studies/S-EPMC5065605biostudies-literatureThe second report of a new hypomyelinating disease due to a defect in the VPS11 gene discloses a massive lysosomal involvement.PMC5065605Krageloh-Mann Idu Bois GHortnagel KBornemann AHarzer KDocker MMayrhofer HBiskup SBattke FfalseThe second report of a new hypomyelinating disease due to a defect in the VPS11 gene discloses a massive lysosomal involvement.Vesicular protein sorting-associated proteins (VPS, including VPS11) are indispensable in the endocytic network, in particular the endosome-lysosome biogenesis. Exome sequencing revealed the homozygous variant p.Leu387_ Gly395del in the VPS11 gene in two siblings. On immunoblotting, the mutant VPS11 protein showed a distinctly reduced immunostaining intensity. The children presented with primary and severe developmental delay associated with myoclonic seizures, spastic tetraplegia, trunk and neck hypotonia, blindness, hearing loss, and microcephaly. Neuro-imaging showed severe hypomyelination affecting cerebral and cerebellar white matter and corpus callosum, in the absence of a peripheral neuropathy. Electron microscopy of a skin biopsy revealed clusters of membranous cytoplasmic bodies i2016-01-01T00:00:00Z2016 Nov2025-04-04T19:38:54.585Z2019-03-27T02:26:45ZS-EPMC50656052747312810.1007/s10545-016-9961-x