Mendelian Susceptibility to Mycobacterial Disease (MSMD): Clinical and Genetic Features of 32 Iranian Patients
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ORIGINAL ARTICLE
Mendelian Susceptibility to Mycobacterial Disease (MSMD): Clinical and Genetic Features of 32 Iranian Patients Seyed Alireza Mahdaviani 1 & Davood Mansouri 1,2,3 & Mahnaz Jamee 1,4,5 & Majid Zaki-Dizaji 6,7 & Karim Rahimi Aghdam 1 & Esmail Mortaz 2 & MirHojjat Khorasanizadeh 7 & Mahsa Eskian 7 & Mahshid Movahedi 1 & Hosseinali Ghaffaripour 1 & Nooshin Baghaie 1 & Maryam Hassanzad 1 & Zahra Chavoshzadeh 8 & Mahboubeh Mansouri 8 & Mehrnaz Mesdaghi 8 & Mehdi Ghaini 1 & Farzad Noori 1 & Shabnam Eskandarzadeh 1 & Shahram Kahkooi 9 & Mihan Poorabdolah 10 & Payam Tabarsi 2 & Afshin Moniri 2 & Parisa Farnia 9 & Abdollah Karimi 11 & Stéphanie Boisson-Dupuis 14,15 & Nima Rezaei 12,13 & Majid Marjani 2 & Jean-Laurent Casanova 14,15,16,17 & Jacinta Bustamante 14,15,18 & Ali Akbar Velayati 1 Received: 7 December 2019 / Accepted: 23 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare congenital condition characterized by a selective predisposition to infections caused by weakly virulent mycobacteria and other types of intra-macrophagic pathogens. The 16 genes associated with MSMD display a considerable level of allelic heterogeneity, accounting for 31 distinct disorders with variable clinical presentations and prognosis. Most of MSMD deficiencies are isolated, referred to as selective susceptibility to mycobacterial diseases. However, other deficiencies are syndromic MSMD, defined by the combination of the mycobacterial infection with another, equally common, infectious, specific phenotypes. Herein, we described a series of 32 Iranian MSMD cases identified with seven distinct types of molecular defects, all of which are involved in the interferon gamma (IFNγ) immunity, including interleukin IL-12 receptor-β1 (IL-12Rβ1) deficiency (fifteen cases), IL-12p40 deficiency (ten cases), and IL-23R deficiency (three cases), as well as IFNγ receptor 1 (IFNγR1) deficiency, IFNγ receptor 2 (IFNγR2) deficiency, interferonstimulated gene 15 (ISG15) deficiency, and tyrosine kinase 2 (TYK2) deficiency each in one case. Since the first report of two MSMD patients in our center, we identified 30 other affected patients with similar clinical manifestations. As the number of reported Iranian cases with MSMD diagnosis has increased in recent years and according to the national vaccination protocol, all Iranian newborns receive BCG vaccination at birth, early diagnosis, and therapeutic intervention which are required for a better outcome and also prevention of similar birth defects. Therefore, we investigated the clinical and molecular features of these 32 patients. The current report also defined novel classes of pathological mutations, further expanding our knowledge of the MSMD molecular basis and associated clinical manifestations. Keywords Mendelian susceptibility to mycobacterial diseases . MSMD . primary immunodeficiency . mycobacteria . BCG . Salmonella
Introduction Mendelian susceptibility to mycobacterial diseases (MSM
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