Article
A pleiotropic recurrent dominant ITPR3 variant causes a complex multisystemic disease.
Science advances - 13 Sept 2024
Molitor Anne, Lederle Alexandre, Radosavljevic Mirjana, Sapuru Vinay, Zavorka Thomas Megan E, Yang Jianying, Shirin Mahsa, Collin-Bund Virginie, Jerabkova-Roda Katerina, Miao Zhichao, Bernard Alice, Rolli Véronique, Grenot Pierre, Castro Carla Noemi, Rosenzwajg Michelle, Lewis Elyssa G, Person Richard, Esperón-Moldes Uxía-Saraiva, Kaare Milja, Nokelainen Pekka T, Batzir Nurit Assia, Hoffer Gal Zaks, Paul Nicodème, Stemmelen Tristan, Naegely Lydie, Hanauer Antoine, Bibi-Triki Sabrina, Grün Sarah, Jung Sophie, Busnelli Ignacio, Tripolszki Kornelia, Al-Ali Ruslan, Ordonez Natalia, Bauer Peter, Song Eunkyung, Zajo Kristin, Partida-Sanchez Santiago, Robledo-Avila Frank, Kumanovics Attila, Louzoun Yoram, Hirschler Aurélie, Pichot Angélique, Toker Ori, Mejía Cesar Andrés Muñoz, Parvaneh Nima, Knapp Esther, Hersh Joseph H, Kenney Heather, Delmonte Ottavia M, Notarangelo Luigi D, Goetz Jacky G, Kahwash Samir B, Carapito Christine, Bajwa Rajinder P S, Thomas Caroline, Ehl Stephan, Isidor Bertrand, Carapito Raphael, Abraham Roshini S, Hite Richard K, Marcus Nufar, Bertoli-Avella Aida, Bahram Seiamak
Abstract excerpt
Inositol 1,4,5-trisphosphate (IP3) receptor type 1 (ITPR1), 2 (ITPR2), and 3 (ITPR3) encode the IP3 receptor (IP3R), a key player in intracellular calcium release. In four unrelated patients, we report that an identical ITPR3 de novo variant-NM_002224.3:c.7570C>T, p.Arg2524Cys-causes, through a dominant-negative effect, a complex multisystemic disorder with immunodeficiency. This leads to defective calcium...