Stankiewicz-Isidor syndrome: expanding the clinical and molecular phenotype.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Isidor Bertrand, Ebstein Frédéric, Hurst Anna, Vincent Marie, Bader Ingrid, Rudy Natasha L, Cogne Benjamin, Mayr Johannes, Brehm Anja, Bupp Caleb, Warren Kathryn, Bacino Carlos A, Gerard Amanda, Ranells Judith D, Metcalfe Kay A, van Bever Yolande, Jiang Yong-Hui, Mendelssohn Bryce A, Cope Heidi, Rosenfeld Jill A, Blackburn Patrick R, Goodenberger McKinsey L, Kearney Hutton M, Kennedy Joanna, Scurr Ingrid, Szczaluba Krzysztof, Ploski Rafal, de Saint Martin Anne, Alembik Yves, Piton Amélie, Bruel Ange-Line, Thauvin-Robinet Christel, Strong Alanna, Diderich Karin E M, Bourgeois Dominique, Dahan Karin, Vignard Virginie, Bonneau Dominique, Colin Estelle, Barth Magalie, Camby Caroline, Baujat Geneviève, Briceño Ignacio, Gómez Alberto, Deb Wallid, Conrad Solène, Besnard Thomas, Bézieau Stéphane, Krüger Elke, Küry Sébastien, Stankiewicz PaweƗ
Аннотация
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.