%0 Generic
%A Isidor B.
%A Ebstein F.
%A Hurst A.
%A Vincent M.
%A Bader I.
%A Rudy N.L.
%A Cogne B.
%A Mayr J.
%A Brehm A.
%A Bupp C.
%A Warren K.
%A Bacino C.A.
%A Gerard A.
%A Ranells J.D.
%A Metcalfe K.A.
%A van Bever Y.
%A Jiang Y.-H.
%A Mendelssohn B.A.
%A Cope H.
%A Rosenfeld J.A.
%A Blackburn P.R.
%A Goodenberger M.L.
%A Kearney H.M.
%A Kennedy J.
%A Scurr I.
%A Szczaluba K.
%A Ploski R.
%A de Saint Martin A.
%A Alembik Y.
%A Piton A.
%A Bruel A.-L.
%A Thauvin-Robinet C.
%A Strong A.
%A Diderich K.E.M.
%A Bourgeois D.
%A Dahan K.
%A Vignard V.
%A Bonneau D.
%A Colin E.
%A Barth M.
%A Camby C.
%A Baujat G.
%A Briceño I.
%A Gómez A.
%A Deb W.
%A Conrad S.
%A Besnard T.
%A Bézieau S.
%A Krüger E.
%A Küry S.
%A Stankiewicz P.
%8 2022
%@ 10983600
%U http://hdl.handle.net/10818/60077
%X 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
%I Genetics in Medicine
%T Stankiewicz-Isidor syndrome: expanding the clinical and molecular phenotype
%R 10.1016/j.gim.2021.09.005
%~ Intellectum