Inborn errors of DNA repair or replication underlie a variety of clinical phenotypes. We studied 5 patients from 4 kindreds, all of whom displayed intrauterine growth retardation, chronic neutropenia, and NK cell deficiency. Four of the 5 patients also had postnatal growth retardation. The association of neutropenia and NK cell deficiency, which is unusual among primary immunodeficiencies and bone marrow failures, was due to a blockade in the bone marrow and was mildly symptomatic. We discovered compound heterozygous rare mutations in Go-Ichi-Ni-San (GINS) complex subunit 1 (
Julien Cottineau, Molly C. Kottemann, Francis P. Lach, Young-Hoon Kang, Frédéric Vély, Elissa K. Deenick, Tomi Lazarov, Laure Gineau, Yi Wang, Andrea Farina, Marie Chansel, Lazaro Lorenzo, Christelle Piperoglou, Cindy S. Ma, Patrick Nitschke, Aziz Belkadi, Yuval Itan, Bertrand Boisson, Fabienne Jabot-Hanin, Capucine Picard, Jacinta Bustamante, Céline Eidenschenk, Soraya Boucherit, Nathalie Aladjidi, Didier Lacombe, Pascal Barat, Waseem Qasim, Jane A. Hurst, Andrew J. Pollard, Holm H. Uhlig, Claire Fieschi, Jean Michon, Vladimir P. Bermudez, Laurent Abel, Jean-Pierre de Villartay, Frédéric Geissmann, Stuart G. Tangye, Jerard Hurwitz, Eric Vivier, Jean-Laurent Casanova, Agata Smogorzewska, Emmanuelle Jouanguy
GINS1 mutations are associated with poor ATR pathway activation.