@misc{10818/60077,
year = {2022},
url = {http://hdl.handle.net/10818/60077},
abstract = {Purpose: Haploinsufficiency of PSMD12 has been reported in individuals with neurodevelopmental phenotypes, including developmental delay/intellectual disability (DD/ID), facial dysmorphism, and congenital malformations, defined as Stankiewicz-Isidor syndrome (STISS). Investigations showed that pathogenic variants in PSMD12 perturb intracellular protein homeostasis. Our objective was to further explore the clinical and molecular phenotypic spectrum of STISS. Methods: We report 24 additional unrelated patients with STISS with various truncating single nucleotide variants or copy-number variant deletions involving PSMD12. We explore disease etiology by assessing patient cells and CRISPR/Cas9-engineered cell clones for various cellular pathways and inflammatory status. Results: The expressivity of most clinical features in STISS is highly variable. In addition to previously reported DD/ID, speech delay, cardiac and renal anomalies, we also confirmed preaxial hand abnormalities as a feature of this syndrome. Of note, 2 patients also showed chilblains resembling signs observed in interferonopathy. Remarkably, our data show that STISS patient cells exhibit a profound remodeling of the mTORC1 and mitophagy pathways with an induction of type I interferon-stimulated genes. Conclusion: We refine the phenotype of STISS and show that it can be clinically recognizable and biochemically diagnosed by a type I interferon gene signature. © 2021 American College of Medical Genetics and Genomics},
publisher = {Genetics in Medicine},
title = {Stankiewicz-Isidor syndrome: expanding the clinical and molecular phenotype},
doi = {10.1016/j.gim.2021.09.005},
author = {Isidor B. and Ebstein F. and Hurst A. and Vincent M. and Bader I. and Rudy N.L. and Cogne B. and Mayr J. and Brehm A. and Bupp C. and Warren K. and Bacino C.A. and Gerard A. and Ranells J.D. and Metcalfe K.A. and van Bever Y. and Jiang Y.-H. and Mendelssohn B.A. and Cope H. and Rosenfeld J.A. and Blackburn P.R. and Goodenberger M.L. and Kearney H.M. and Kennedy J. and Scurr I. and Szczaluba K. and Ploski R. and de Saint Martin A. and Alembik Y. and Piton A. and Bruel A.-L. and Thauvin-Robinet C. and Strong A. and Diderich K.E.M. and Bourgeois D. and Dahan K. and Vignard V. and Bonneau D. and Colin E. and Barth M. and Camby C. and Baujat G. and Briceño I. and Gómez A. and Deb W. and Conrad S. and Besnard T. and Bézieau S. and Krüger E. and Küry S. and Stankiewicz P.},
}