Academic Journal
Geleophysic dysplasia: novel missense variants and insights into ADAMTSL2 intracellular trafficking
| العنوان: | Geleophysic dysplasia: novel missense variants and insights into ADAMTSL2 intracellular trafficking |
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| المؤلفون: | Piccolo, Pasquale, Sabatino, Valeria, Mithbaokar, Pratibha, Polishchucka, Elena, Law, Simon K., Magraner-Pardo, Lorena, Pons, Tirso, Polishchuck, Roman, Brunetti-Pierri, Nicola |
| المساهمون: | Fondazione Telethon |
| بيانات النشر: | Elsevier Academic Press |
| سنة النشر: | 2019 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | Geleophysic dysplasia, ADAMTSL2, Connective tissue disorder, TGF-β signaling |
| الوصف: | Geleophysic dysplasia (GPHYSD1, MIM231050; GPHYSD2, MIM614185; GPHYSD3, MIM617809) is an autosomal disorder characterized by short-limb dwarfism, brachydactyly, cardiac valvular disease, and laryngotracheal stenosis. Mutations in ADAMTSL2, FBN1, and LTBP3 genes are responsible for this condition. We found that three previously described cases of GPHYSD diagnosed clinically were homozygote or compound heterozygotes for five ADAMTSL2 variants, four of which not being previously reported. By electron microscopy, skin fibroblasts available in one case homozygote for an ADAMTSL2 variant showed a defective intracellular localization of mutant ADAMTSL2 protein that did not accumulate within lysosome-like intra-cytoplasmic inclusions. Moreover, this mutant ADAMTSL2 protein was less secreted in medium and resulted in increased SMAD2 phosphorylation in transfected HEK293 cells. ; This work was supported by Fondazione Telethon, Italy (TCBP37TELC and TCBMT3TELD) to N.B.-P. We are grateful to John Tolmie for providing DNA sample of one the cases |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 1096-7192 |
| Relation: | Publisher's version; http://dx.doi.org/10.1016/j.ymgmr.2019.100504; Sí; Molecular Genetics and Metabolism Reports 21: 100504 (2019); http://hdl.handle.net/10261/240365; http://dx.doi.org/10.13039/501100002426 |
| DOI: | 10.1016/j.ymgmr.2019.100504 |
| DOI: | 10.13039/501100002426 |
| الاتاحة: | http://hdl.handle.net/10261/240365 https://doi.org/10.1016/j.ymgmr.2019.100504 https://doi.org/10.13039/501100002426 |
| Rights: | open |
| رقم الانضمام: | edsbas.4F465645 |
| قاعدة البيانات: | BASE |
| تدمد: | 10967192 |
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| DOI: | 10.1016/j.ymgmr.2019.100504 |