{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:05:35Z","timestamp":1790687135667,"version":"4.1.0"},"reference-count":14,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,7,29]],"date-time":"2016-07-29T00:00:00Z","timestamp":1469750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,7,29]],"date-time":"2016-07-29T00:00:00Z","timestamp":1469750400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Vesicular protein sorting\u2010associated proteins (VPS, including VPS11) are indispensable in the endocytic network, in particular the endosome\u2010lysosome biogenesis. Exome sequencing revealed the homozygous variant p.Leu387_ Gly395del in the <jats:italic>VPS11<\/jats:italic> 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\u2010imaging 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 in dermal unmyelinated nerve axons, and numbers of vacuoles in eccrine sweat glands, similar to what is seen in a classic lysosomal storage disease (LSD). Bone marrow cytology showed a high number of storage macrophages with a micro\u2010vacuolated cytoplasm. Biochemically, changes in urinary glycosphingolipids were reminiscent of those in prosaposin deficiency (another LSD). The clinical and neuro\u2010imaged features in our patients were almost identical to those in some recently reported patients with another variant in the <jats:italic>VPS11<\/jats:italic> gene, p.Cys846Gly; underlining the presumed pathogenic potential of <jats:italic>VPS11<\/jats:italic> defects. A new feature was the morphological evidence for lysosomal storage in VPS11 deficiency: This newly characterised disease can be viewed as belonging to the complex field of LSD.<\/jats:p>","DOI":"10.1007\/s10545-016-9961-x","type":"journal-article","created":{"date-parts":[[2016,7,29]],"date-time":"2016-07-29T07:42:56Z","timestamp":1469778176000},"page":"849-857","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["The second report of a new hypomyelinating disease due to a defect in the <i>VPS11<\/i> gene discloses a massive lysosomal involvement"],"prefix":"10.1002","volume":"39","author":[{"given":"Konstanze","family":"H\u00f6rtnagel","sequence":"first","affiliation":[{"name":"Praxis f\u00fcr Humangenetik Paul\u2010Ehrlich\u2010Str. 23 T\u00fcbingen 72076 Germany"},{"name":"CeGaT GmbH Paul\u2010Ehrlich\u2010Str. 23 T\u00fcbingen 72076 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Kr\u00e4geloh\u2010Mann","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics and Neurometabolic Laboratory Children's Hospital of the University of T\u00fcbingen Hoppe\u2010Seyler\u2010Str. 1 T\u00fcbingen 72076 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Bornemann","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Neuropathology University of T\u00fcbingen Calwer Str. 3 T\u00fcbingen 72076 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"D\u00f6cker","sequence":"additional","affiliation":[{"name":"Praxis f\u00fcr Humangenetik Paul\u2010Ehrlich\u2010Str. 23 T\u00fcbingen 72076 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Biskup","sequence":"additional","affiliation":[{"name":"Praxis f\u00fcr Humangenetik 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