Patient with an autosomal-recessive MBTPS1-linked phenotype and clinical features of Silver-Russell syndrome.
MBTPS1
Silver-Russell syndrome
pathogenic variant
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
12
05
2020
revised:
28
07
2020
accepted:
02
08
2020
pubmed:
29
8
2020
medline:
22
6
2021
entrez:
29
8
2020
Statut:
ppublish
Résumé
Pathogenic variants in the MBTPS1 gene encoding the Site 1 protease have been described so far only in one growth retarded patients with skeletal deformities, large ears, a triangular face reminiscent to Silver-Russell syndrome (SRS), and elevated blood lysosomal enzymes. We now report on the identification of a second adult patient homozygous for one of the two published pathogenic MBTPS1 variants (p.Asp365Gly) by Whole Exome Sequencing (WES), and a comparable phenotype. With this case, the association of pathogenic variants in MBTPS1 with a recognizable disorder could be confirmed, and the autosomal recessive inheritance is further established. As the variant was identified after a long diagnostic odyssey of the family, this example illustrates the need to apply WES in the diagnostic workup in case of growth retardation as early as possible. By compiling the clinical data of this new patient with those of the already reported patient, a better prognosis for future patients with MBTPS1 variants can be issued, and clinical management can be adjusted.
Identifiants
pubmed: 32857899
doi: 10.1002/ajmg.a.61833
doi:
Substances chimiques
Proprotein Convertases
EC 3.4.21.-
Serine Endopeptidases
EC 3.4.21.-
membrane-bound transcription factor peptidase, site 1
EC 3.4.21.112
Types de publication
Case Reports
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2727-2730Informations de copyright
© 2020 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
Références
Brown, M. S., & Goldstein, J. L. (1997). The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell, 89(3), 331-340. https://doi.org/10.1016/s0092-8674(00)80213-5
Civallero, G., Michelin, K., de Mari, J., Viapiana, M., Burin, M., Coelho, J. C., & Giugliani, R. (2006). Twelve different enzyme assays on dried-blood filter paper samples for detection of patients with selected inherited lysosomal storage diseases. Clinica Chimica Acta, 372(1-2), 98-102. https://doi.org/10.1016/j.cca.2006.03.029
Kondo, Y., Fu, J., Wang, H., Hoover, C., McDaniel, J. M., Steet, R., … Xia, L. (2018). Site-1 protease deficiency causes human skeletal dysplasia due to defective inter-organelle protein trafficking. JCI Insight, 3(14), e121596. https://doi.org/10.1172/jci.insight.121596
Marschner, K., Kollmann, K., Schweizer, M., Braulke, T., & Pohl, S. (2011). A key enzyme in the biogenesis of lysosomes is a protease that regulates cholesterol metabolism. Science, 333(6038), 87-90. https://doi.org/10.1126/science.1205677
Meyer, R., Soellner, L., Begemann, M., Dicks, S., Fekete, G., Rahner, N., … Eggermann, T. (2017). Targeted next generation sequencing approach in patients referred for Silver-Russell syndrome testing increases the mutation detection rate and provides decisive information for clinical management. The Journal of Pediatrics, 187(206-212), e201. https://doi.org/10.1016/j.jpeds.2017.04.018
Schweitzer, G. G., Gan, C., Bucelli, R. C., Wegner, D., Schmidt, R. E., Shinawi, M., … Brookheart, R. T. (2019). A mutation in Site-1 protease is associated with a complex phenotype that includes episodic hyperCKemia and focal myoedema. Molecular Genetics & Genomic Medicine, 7(7), e00733. https://doi.org/10.1002/mgg3.733
Sewell, A. C., Haskins, M. E., & Giger, U. (2012). Dried blood spots for the enzymatic diagnosis of lysosomal storage diseases in dogs and cats. Veterinary Clinical Pathology, 41(4), 548-557. https://doi.org/10.1111/j.1939-165x.2012.00485.x
Tumer, Z., Lopez-Hernandez, J. A., Netchine, I., Elbracht, M., Gronskov, K., Gede, L. B., … Eggermann, T. (2018). Structural and sequence variants in patients with Silver-Russell syndrome or similar features-Curation of a disease database. Human Mutation, 39(3), 345-364. https://doi.org/10.1002/humu.23382
Wakeling, E. L., Brioude, F., Lokulo-Sodipe, O., O'Connell, S. M., Salem, J., Bliek, J., … Netchine, I. (2017). Diagnosis and management of Silver-Russell syndrome: First international consensus statement. Nature Reviews. Endocrinology, 13(2), 105-124. https://doi.org/10.1038/nrendo.2016.138