Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Case Report: Reactive Lymphohistiocytic Proliferation in Infant With a Novel Nonsense Variant of IL2RG Who Received BCG Vaccine

ABSTRACT: We present here a male young infant with X-linked severe combined immunodeficiency (MIM#300400) due to the novel nonsense variant of IL2RG (interleukin 2 receptor, gamma; MIM#308380), NM_000206.2(IL2RG):c.820_823dup p.Ser275Asnfs*29. He developed aggressive reactive lymphohistiocytic proliferation after receiving the live-attenuated Bacillus Calmette-Guérin (BCG) vaccine at birth. This report advocates for modifying the current practice of early use of BCG. The natural history of his disease also suggests considering IL2RG variants as a potential cause of “X-linked recessive Mendelian susceptibility to mycobacterial disease” (MSMD). His reactive lymphohistiocytic proliferation and massive hepatosplenomegaly simulated hemophagocytic lymphohistiocytosis (HLH, likely triggered by the BCG disease). This entity was masked by the absence of fever and markedly elevated inflammatory biomarkers. Thus, his findings stimulate discussion on the need to modify the diagnostic criteria of HLH, in order to accommodate conditions, such IL2RG variants that block systemic inflammation.

SUBMITTER: Yahya A

PROVIDER: S-EPMC8592917 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Family-Based Next-Generation Sequencing Study Identifies an IL2RG Variant in an Infant with Primary Immunodeficiency.

Project description:Primary immunodeficiencies (PIDs) are a rare and heterogeneous group of inherited genetic disorders that are characterized by an absent or impaired immune system. In this report, we describe the use of next-generation sequencing to investigate a male infant with clinical and immunological manifestations suggestive of a PID. Whole-exome sequencing of the infant along with his parents revealed a novel nucleotide variant (cytosine to adenine substitution at nucleotide position 252) in the coding region of the interleukin 2 receptor subunit gamma (IL2RG) gene. The mother was found to be a carrier. These findings are consistent with a diagnosis of X-linked severe combined immunodeficiency and represent the first such reported mutation in an Indian family. This mutation leads to an asparagine to lysine substitution ( p.Asn84Lys ) located in the extracellular domain of IL2RG, which is predicted to be pathogenic. Our study demonstrates the power of next-generation sequencing in identifying potential causative mutations to enable accurate clinical diagnosis, prenatal screening, and carrier female detection in PID patients. We believe that this approach, which is not a current routine in clinical practice, will become a mainstream component of individualized medicine in the near future.

| S-EPMC6534087 | biostudies-literature

Case Report: Complete Maternal Uniparental Isodisomy of Chromosome 5 (iUPD(5)mat) With PCSK1 Nonsense Variant in an Infant With Recurrent Diarrhea.

Project description:Congenital diarrhea diseases are a heterogeneous group of conditions and are the major cause of neonatal mortality worldwide. Proprotein convertase 1/3 (PC1/3) deficiency has been associated with severe malabsorptive diarrhea, obesity, and certain endocrine abnormalities. We report an infant born to non-consanguineous parents who is diagnosed with PC1/3 deficiency due to nonsense homozygous variant (c.238 C>T, p.Arg80Ter) in the PCSK1 gene, identified by Trio-exome sequencing (Trio-ES). The baby girl presented with recurrent diarrhea, transient liver dysfunction and hypoglycemia. Trio-ES showed complete maternal uniparental isodisomy (iUPD) of chromosome 5. Our finding provides accurate genetic counseling to this family and expands the clinical spectrum of iUPD with pathogenic variants causing recessive disease.

| S-EPMC8134681 | biostudies-literature

Lessons learnt from the first efficacy trial of a new infant tuberculosis vaccine since BCG.

Project description:BACKGROUND:New tuberculosis (TB) vaccines are being developed to combat the global epidemic. A phase IIb trial of a candidate vaccine, MVA85A, was conducted in a high burden setting in South Africa to evaluate proof-of-concept efficacy for prevention of TB in infants. OBJECTIVE:To describe the study design and implementation lessons from an infant TB vaccine efficacy trial. METHODS:This was a randomised, controlled, double-blind clinical trial comparing the safety and efficacy of MVA85A to Candin control administered to 4-6-month-old, BCG-vaccinated, HIV-negative infants at a rural site in South Africa. Infants were followed up for 15-39 months for incident TB disease based on pre-specified endpoints. RESULTS:2797 infants were enrolled over 22 months. Factors adversely affecting recruitment and the solutions that were implemented are discussed. Slow case accrual led to six months extension of trial follow up. CONCLUSION:The clinical, regulatory and research environment for modern efficacy trials of new TB vaccines are substantially different to that when BCG vaccine was first evaluated in infants. Future infant TB vaccine trials will need to allocate sufficient resources and optimise operational efficiency. A stringent TB case definition is necessary to maximize specificity, and TB case accrual must be monitored closely.

| S-EPMC3608032 | biostudies-literature

BCG vaccine strains

Project description:Mapping the phylogeny and lineage history of geographically distinct BCG vaccine strains

| PRJEB55451 | ENA

Case Report: Preimplantation Genetic Testing for X-Linked Severe Combined Immune Deficiency Caused by IL2RG Gene Variant.

Project description:Preimplantation genetic testing (PGT) has been increasingly used to prevent rare inherited diseases. In this study, we report a case where PGT was used to prevent the transmission of disease-caused variant in a SCID-X1 (OMIM:300400) family. SCID-X1 is an X-linked recessive inherited disease whose major clinical manifestation of immune deficiency is the significant reduction in the number of T-cells and natural killer cells. This family gave birth to a boy who was a hemizygous proband whose IL2RG gene was mutated (c.315T > A, p(Tyr105*), NM_000206.3, CM962677). In this case, Sanger sequencing for mutated allele and linkage analysis based on single-nucleotide polymorphism (SNP) haplotype via next-generation sequencing were performed simultaneously. After PGT for monogenic disorder, we detected the aneuploidy and copy number variation (CNV) for normal and female carrier embryos. Four embryos (E02, E09, E10, and E11) were confirmed without CNVs and inherited variants at the IL2RG gene. Embryo E02 (ranking 4BB) has been transferred after considering the embryo growth rate, morphology, and PGT results. Prenatal genetic diagnosis was used to detect amniotic fluid cells, showing that this fetus did not carry the variant of the IL2RG gene (c.315T > A). Ultimately, a healthy girl who had not carried disease-causing variants of SCID-X1 confirmed by prenatal diagnosis was born, further verifying our successful application of PGT in preventing mutated allele transmission for this SCID family.

| S-EPMC9198258 | biostudies-literature

Case Report: BCG-Triggered Hemophagocytic Lymphohistiocytosis in an Infant With X-Linked Recessive Mendelian Susceptibility to Mycobacterial Disease Due to a Variant of Chronic Granulomatous Disease.

Project description:In the United Arab Emirates, BCG (Bacillus Calmette-Guérin) is administered to all newborns. We present here a young infant with an inborn error of immunity (IEI) who developed fatal adverse events to this live-attenuated vaccine. This male infant received BCG (Serum Institute of India Pvt., Ltd., India) on Day 11 of life. On Day 25, he developed fever, followed by cervical lymphadenitis and bilateral otitis media with fluid drainage. On Day 118, he was admitted with severe hemophagocytic lymphohistiocytosis (HLH), and passed away on Day 145. The diagnostic exome sequencing test identified a hemizygous nonsense variant, NM_000397.3(CYBB):c.676C>T, p.Arg226* (rs137854592). Pathogenic variants of CYBB [cytochrome b(-245), beta subunit; Mendelian Inheritance in Man [MIM] accession code, 300481] are known to cause "immunodeficiency 34, mycobacteriosis, X-linked" (IMD34, MIM#300645) and "chronic granulomatous disease, X-linked" (CGDX, MIM#306400). The natural history of his illness is consistent with "X-linked recessive Mendelian susceptibility to mycobacterial disease (MSMD)." This entity is responsible for his BCG disease and is a likely trigger of his HLH. This disastrous event underlines the importance of developing worldwide policies that target BCG disease prevention, especially in communities with high prevalence of IEI. Moreover, screening for genetic causes of MSMD in the community could pave the way, at least partially, for scale-up of tuberculosis (TB) prevention.

| S-EPMC8275851 | biostudies-literature

BCG vaccine in Korea.

Project description:The anti-tuberculosis Bacille de Calmette et Guérin (BCG) vaccine was developed between 1905 and 1921 at Pasteur Institutes of Lille in France, and was adopted by many countries. BCG strains comprise natural mutants of major virulence factors of Mycobacterium tuberculosis and that BCG sub-strains differ markedly in virulence levels. The tuberculosis became endemic in Korea after the Korean War (1950s). The BCG strain, which was donated by Pasteur Institutes, was brought to Korea in 1955, and the first domestic BCG vaccine was produced by the National Defense Research Institute (NDRI), current Korea Centers for Disease Control and Prevention (KCDC), in 1960. Since 1987, BCG manufacture work was handed over to the Korean Institute of Tuberculosis (KIT), the freeze-dried BCG vaccine was manufactured at a scale required to meet the whole amount of domestic consumption. However, since 2006, the manufacture of BCG vaccine suspended and the whole amount of BCG was imported at this point of time. Now KIT is planning to re-produce the BCG vaccine in Korea under the supervision of KCDC, this will be render great role to National Tuberculosis Control Program (NTP) and provide initiating step for developing new tuberculosis vaccines in Korea.

| S-EPMC3710928 | biostudies-literature

Novel ERCC2 variant in trichothiodystrophy infant: the first case report in China.

Project description:BackgroundTrichothiodystrophy (TTD) is a rare, autosomal recessive, multisystem disorder most commonly caused by variants in ERCC2.Case presentationHere, we describe the first Chinese patient with a novel variant in ERCC2. A male infant, who was born to a healthy non-consanguineous couple, exhibited brittle hair, hair loss ichthyosis, eczema, retinal pigmentation and hypospadias. He carried a novel heterozygous ERCC2 variant. The maternal variant (c.2191-18_2213del) is a previous described genomic deletion that affects the splicing of intron 22. The paternal variant (c.1666-1G?>?A), that occurs in the splice site of intron 17 and likely alters ERCC2 gene function through aberrant splicing, has not been reported previously.ConclusionsOur case reported a novel pathogenic variant in ERCC2, which expanded the known genetic variants associated with TTD.

| S-EPMC7955621 | biostudies-literature

A novel nonsense PTH1R variant shows incomplete penetrance of primary failure of eruption: a case report.

Project description:BACKGROUND:Aim of this work was to describe a rare inheritance pattern of Primary Failure of Eruption (PFE) in a small family with incomplete penetrance of PFE and a novel nonsense PTH1R variant. CASE PRESENTATION:The proband, a 26?year-old man with a significant bilateral open-bite, was diagnosed with PFE using clinical and radiographic characteristics. DNA was extracted from the proband and his immediate family using buccal swabs and the entire PTH1R coding sequence was analyzed, revealing a novel heterozygous nonsense variant in exon 7 of PTH1R (c.505G?>?T). This variant introduces a premature stop codon in position 169, predicted to result in the production of a truncated and non-functional protein. This variant has never been reported in association with PFE and is not present in the Genome Aggregation Database (gnomAD). Interestingly, the c.505G?>?T variant has also been identified in the unaffected mother of our proband, suggesting incomplete penetrance of PFE. CONCLUSIONS:In this study, we report a new PTH1R variant that segregates in an autosomal dominant pattern and causes PFE with incomplete penetrance. This underlines the diagnostic value of a thorough clinical and genetic analysis of all family members in order to estimate accurate recurrence risks, identify subtle clinical manifestations and provide proper management of PFE patients.

| S-EPMC6858648 | biostudies-literature

BCG vaccine may generate cross-reactive T cells against SARS-CoV-2: In silico analyses and a hypothesis.

Project description:The world is facing the rising emergency of SARS-CoV-2. The outbreak of COVID-19 has caused a global public health and economic crisis.Recent epidemiological studies have shown that a possible association of BCG vaccination program with decreased COVID-19-related risks, suggesting that BCG may provide protection against COVID-19. Non-specific protection against viral infections is considered as a main mechanism of BCG and clinical trials to determine whether BCG vaccine can protect healthcare workers from the COVID-19 are currently underway. We hypothesized that BCG may carry similar T cell epitopes with SARS-CoV-2 and evaluated the hypothesis by utilizing publicly available database and computer algorithms predicting human leukocyte antigen (HLA) class I-binding peptides. We foundthatBCG contains similar 9-amino acid sequences with SARS-CoV-2. These closely-related peptides had moderate to high binding affinity for multiple common HLA class I molecules, suggesting that cross-reactive T cells against SARS-CoV-2 could be generated by BCG vaccination.

| S-EPMC7440160 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data