Next generation sequencing analysis of consecutive Russian patients with clinical suspicion of inborn errors of immunity.
Adolescent
Agammaglobulinemia
/ genetics
CHARGE Syndrome
/ genetics
Child
Child, Preschool
DNA-Binding Proteins
/ deficiency
Endonucleases
/ deficiency
Female
Genetic Diseases, X-Linked
/ genetics
Genetic Predisposition to Disease
High-Throughput Nucleotide Sequencing
Humans
Infant
Male
Primary Immunodeficiency Diseases
/ genetics
Russia
/ epidemiology
Semaphorins
/ genetics
Severe Combined Immunodeficiency
/ genetics
Transcription Factors
/ deficiency
AIRE Protein
children
inborn errors of immunity
mutation
next generation sequencing
primary immunodeficiency
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
15
01
2020
revised:
12
05
2020
accepted:
15
05
2020
pubmed:
23
5
2020
medline:
13
7
2021
entrez:
23
5
2020
Statut:
ppublish
Résumé
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.
Substances chimiques
DNA-Binding Proteins
0
SEMA3E protein, human
0
Semaphorins
0
Transcription Factors
0
DCLRE1C protein, human
EC 3.1.-
Endonucleases
EC 3.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
231-239Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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