Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Sep;98(3):231-239.
doi: 10.1111/cge.13789. Epub 2020 Jun 17.

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

Evgeny N Suspitsin  1   2 , Marina N Guseva  3   4 , Mikhail M Kostik  5 , Anna P Sokolenko  1   2 , Nataliya V Skripchenko  6   7 , Anastasia S Levina  6 , Olga V Goleva  8 , Margarita F Dubko  5 , Anastasia V Tumakova  1 , Maria A Makhova  1 , Lidiya V Lyazina  9 , Ilya V Bizin  2 , Natalia E Sokolova  10 , Tatiana V Gabrusskaya  11 , Liliya V Ditkovskaya  12 , Olga P Kozlova  13 , Svetlana S Vahliarskaya  14 , Irina V Kondratenko  14 , Evgeny N Imyanitov  1   2   15   16
Affiliations

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

Evgeny N Suspitsin et al. Clin Genet. 2020 Sep.

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.

Keywords: children; inborn errors of immunity; mutation; next generation sequencing; primary immunodeficiency.

PubMed Disclaimer

References

REFERENCES

    1. Tangye SG, Al-Herz W, Bousfiha A, et al. Human inborn errors of immunity: 2019 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2020;40:24-64. https://doi.org/10.1007/s10875-019-00737-x.
    1. Arkwright PD, Gennery AR. Ten warning signs of primary immunodeficiency: a new paradigm is needed for the 21st century. Ann N Y Acad Sci. 2011;1238:7-14. https://doi.org/10.1111/j.1749-6632.2011.06206.x.
    1. Bousfiha A, Jeddane L, Picard C, et al. The 2017 IUIS phenotypic classification for primary immunodeficiencies. J Clin Immunol. 2018;38:129-143. https://doi.org/10.1007/s10875-017-0465-8.
    1. Picard C, Bobby Gaspar H, Al-Herz W, et al. International Union of Immunological Societies: 2017 primary immunodeficiency diseases committee report on inborn errors of immunity. J Clin Immunol. 2018;38:96-128. https://doi.org/10.1007/s10875-017-0464-9.
    1. Dantas EO, Aranda CS, Rêgo Silva AM, et al. Doctors’ awareness concerning primary immunodeficiencies in Brazil. Allergol Immunopathol (Madr). 2015;43:272-278. https://doi.org/10.1016/j.aller.2014.09.002.

Publication types

MeSH terms

Supplementary concepts

LinkOut - more resources