1. Next generation sequencing analysis of consecutive Russian patients with clinical suspicion of inborn errors of immunity.
- Author
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Suspitsin EN, Guseva MN, Kostik MM, Sokolenko AP, Skripchenko NV, Levina AS, Goleva OV, Dubko MF, Tumakova AV, Makhova MA, Lyazina LV, Bizin IV, Sokolova NE, Gabrusskaya TV, Ditkovskaya LV, Kozlova OP, Vahliarskaya SS, Kondratenko IV, and Imyanitov EN
- Subjects
- Adolescent, Agammaglobulinemia immunology, Agammaglobulinemia pathology, CHARGE Syndrome immunology, CHARGE Syndrome pathology, Child, Child, Preschool, DNA-Binding Proteins deficiency, DNA-Binding Proteins genetics, DNA-Binding Proteins immunology, Endonucleases deficiency, Endonucleases genetics, Endonucleases immunology, Female, Genetic Diseases, X-Linked immunology, Genetic Diseases, X-Linked pathology, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing, Humans, Infant, Male, Primary Immunodeficiency Diseases immunology, Primary Immunodeficiency Diseases pathology, Russia epidemiology, Semaphorins genetics, Semaphorins immunology, Severe Combined Immunodeficiency immunology, Severe Combined Immunodeficiency pathology, Transcription Factors deficiency, Transcription Factors genetics, Transcription Factors immunology, AIRE Protein, Agammaglobulinemia genetics, CHARGE Syndrome genetics, Genetic Diseases, X-Linked genetics, Primary Immunodeficiency Diseases genetics, Severe Combined Immunodeficiency genetics
- Abstract
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.)
- Published
- 2020
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