The second report of a new hypomyelinating disease due to a defect in the VPS11 gene discloses a massive lysosomal involvement
| العنوان: | The second report of a new hypomyelinating disease due to a defect in the VPS11 gene discloses a massive lysosomal involvement |
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| المؤلفون: | Gabriele du Bois, Miriam Döcker, Antje Bornemann, Florian Battke, Heidi Mayrhofer, Saskia Biskup, Inge Krägeloh-Mann, Klaus Harzer, Konstanze Hörtnagel |
| المصدر: | Journal of Inherited Metabolic Disease |
| بيانات النشر: | Springer Netherlands, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Pathology, medicine.medical_specialty, Microcephaly, Adolescent, Vesicular Transport Proteins, Endosomes, Biology, Cataract, 03 medical and health sciences, Lysosomal storage disease, medicine, Genetics, Humans, Genetics(clinical), Eccrine sweat gland, Child, Genetics (clinical), Base Sequence, medicine.disease, Fabry disease, Hypotonia, Metachromatic leukodystrophy, Lysosomal Storage Diseases, Hereditary Central Nervous System Demyelinating Diseases, 030104 developmental biology, Peripheral neuropathy, medicine.anatomical_structure, Mutation, Original Article, Female, medicine.symptom, Lysosomes, Immunostaining, Demyelinating Diseases |
| الوصف: | 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 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-vacuolated cytoplasm. Biochemically, changes in urinary glycosphingolipids were reminiscent of those in prosaposin deficiency (another LSD). The clinical and neuro-imaged features in our patients were almost identical to those in some recently reported patients with another variant in the VPS11 gene, p.Cys846Gly; underlining the presumed pathogenic potential of VPS11 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. Electronic supplementary material The online version of this article (doi:10.1007/s10545-016-9961-x) contains supplementary material, which is available to authorized users. |
| اللغة: | English |
| تدمد: | 1573-2665 0141-8955 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::71ebb2f1824abf65b24585233c471474 http://europepmc.org/articles/PMC5065605 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....71ebb2f1824abf65b24585233c471474 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15732665 01418955 |
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