Next generation sequencing analysis of consecutive Russian patients with clinical suspicion of inborn errors of immunity.

Autor: Suspitsin EN; Department of Medical Genetics, St. Petersburg State Pediatric Medical University, St. Petersburg, Russia.; Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St. Petersburg, Russia., Guseva MN; Outpatient Department, St. Petersburg State Pediatric Medical University, St. Petersburg, Russia.; Department of Immunology, First Pavlov State Medical University, St. Petersburg, Russia., Kostik MM; Department of Hospital Pediatrics, St. Petersburg State Pediatric Medical University, St. Petersburg, Russia., Sokolenko AP; Department of Medical Genetics, St. Petersburg State Pediatric Medical University, St. Petersburg, Russia.; Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St. Petersburg, Russia., Skripchenko NV; Department of Infectious Diseases in Children, Faculty of Postgraduate Education, St. Petersburg State Pediatric Medical University, St. Petersburg, Russia.; Department of Neuroinfections and Nervous System Pathology, Pediatric Research and Clinical Center for Infectious Diseases, St. Petersburg, Russia., Levina AS; Department of Infectious Diseases in Children, Faculty of Postgraduate Education, St. Petersburg State Pediatric Medical University, St. Petersburg, Russia., Goleva OV; Department of Virusology and Molecular Biology, Pediatric Research and Clinical Center for Infectious Diseases, St. Petersburg, Russia., Dubko MF; Department of Hospital Pediatrics, St. Petersburg State Pediatric Medical University, St. Petersburg, Russia., Tumakova AV; Department of Medical Genetics, St. Petersburg State Pediatric Medical University, St. Petersburg, Russia., Makhova MA; Department of Medical Genetics, St. Petersburg State Pediatric Medical University, St. Petersburg, Russia., Lyazina LV; City Center for Medical Genetics, St. Petersburg, Russia., Bizin IV; Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St. Petersburg, Russia., Sokolova NE; Department of Hematology, First City Children Hospital, St. Petersburg, Russia., Gabrusskaya TV; Department of Gastroenterology, Faculty of Postgraduate Education, St. Petersburg State Pediatric Medical University, St. Petersburg, Russia., Ditkovskaya LV; I.M. Vorontsov Department of Pediatrics, Faculty of Postgraduate Education, St. Petersburg State Pediatric Medical University, St. Petersburg, Russia., Kozlova OP; Department of Clinical Mycology, Allergology and Immunology, I.I. Mechnikov North-Western Medical University, St. Petersburg, Russia., Vahliarskaya SS; Department of Clinical Immunology, Russian Children Clinical Hospital, N.N. Pirogov National Research Medical University, Moscow, Russia., Kondratenko IV; Department of Clinical Immunology, Russian Children Clinical Hospital, N.N. Pirogov National Research Medical University, Moscow, Russia., Imyanitov EN; Department of Medical Genetics, St. Petersburg State Pediatric Medical University, St. Petersburg, Russia.; Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St. Petersburg, Russia.; Department of Oncology, I.I. Mechnikov North-Western Medical University, St. Petersburg, Russia.; Department of Oncology, Saint Petersburg State University, St. Petersburg, Russia.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2020 Sep; Vol. 98 (3), pp. 231-239. Date of Electronic Publication: 2020 Jun 17.
DOI: 10.1111/cge.13789
Abstrakt: Primary immune deficiencies are usually attributed to genetic defects and, therefore, frequently referred to as inborn errors of immunity (IEI). We subjected the genomic DNA of 333 patients with clinical signs of IEI to next generation sequencing (NGS) analysis of 344 immunity-related genes and, in some instances, additional genetic techniques. Genetic causes of the disease were identified in 69/333 (21%) of subjects, including 11/18 (61%) of children with syndrome-associated IEIs, 45/202 (22%) of nonsyndromic patients with Jeffrey Modell Foundation (JMF) warning signs, 9/56 (16%) of subjects with periodic fever, 3/30 (10%) of cases of autoimmune cytopenia, 1/21 (5%) of patients with unusually severe infections and 0/6 (0%) of individuals with isolated elevation of IgE level. There were unusual clinical observations: twins with severe immunodeficiency carried a de novo CHARGE syndrome-associated SEMA3E c.2108C>T (p.S703L) allele; however, they lacked clinical features of CHARGE syndrome. Additionally, there were genetically proven instances of Netherton syndrome, Х-linked agammaglobulinemia, severe combined immune deficiency (SCID), IPEX and APECED syndromes, among others. Some patients carried recurrent pathogenic alleles, such as AIRE c.769C>T (p.R257*), NBN c.657del5, DCLRE1C c.103C>G (p.H35D), NLRP12 c.1054C>T (p.R352C) and c.910C>T (p.H304Y). NGS is a powerful tool for high-throughput examination of patients with malfunction of immunity.
(© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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