Journal article
Vaccine-associated varicella and rubella infections in severe combined immunodeficiency with isolated CD4 lymphocytopenia and mutations in IL7R detected by tandem whole exome sequencing and chromosomal microarray
Clinical and experimental immunology, Vol.178(3), pp.459-469
12/2014
DOI: 10.1111/cei.12421
PMCID: PMC4238873
PMID: 25046553
Abstract
In areas without newborn screening for severe combined immunodeficiency (SCID), disease-defining infections may lead to diagnosis, and in some cases, may not be identified prior to the first year of life. We describe a female infant who presented with disseminated vaccine-acquired varicella (VZV) and vaccine-acquired rubella infections at 13 months of age. Immunological evaluations demonstrated neutropenia, isolated CD4 lymphocytopenia, the presence of CD8
+
T cells, poor lymphocyte proliferation, hypergammaglobulinaemia and poor specific antibody production to VZV infection and routine immunizations. A combination of whole exome sequencing and custom-designed chromosomal microarray with exon coverage of primary immunodeficiency genes detected compound heterozygous mutations (one single nucleotide variant and one intragenic copy number variant involving one exon) within the
IL7R
gene. Mosaicism for wild-type allele (20–30%) was detected in pretransplant blood and buccal DNA and maternal engraftment (5–10%) demonstrated in pretransplant blood DNA. This may be responsible for the patient's unusual immunological phenotype compared to classical interleukin (IL)-7Rα deficiency. Disseminated VZV was controlled with anti-viral and immune-based therapy, and umbilical cord blood stem cell transplantation was successful. Retrospectively performed T cell receptor excision circle (TREC) analyses completed on neonatal Guthrie cards identified absent TREC. This case emphasizes the danger of live viral vaccination in severe combined immunodeficiency (SCID) patients and the importance of newborn screening to identify patients prior to high-risk exposures. It also illustrates the value of aggressive pathogen identification and treatment, the influence newborn screening can have on morbidity and mortality and the significant impact of newer genomic diagnostic tools in identifying the underlying genetic aetiology for SCID patients.
Details
- Title: Subtitle
- Vaccine-associated varicella and rubella infections in severe combined immunodeficiency with isolated CD4 lymphocytopenia and mutations in IL7R detected by tandem whole exome sequencing and chromosomal microarray
- Creators
- D K Bayer - Texas Children's HospitalC A Martinez - Texas Children's HospitalH S Sorte - Oslo University HospitalL R Forbes - Texas Children's HospitalG J Demmler-Harrison - Texas Children's HospitalI C Hanson - Texas Children's HospitalN M Pearson - Baylor College of MedicineL M Noroski - Texas Children's HospitalS R Zaki - Centers for Disease Control and PreventionW J Bellini - National Center for Immunization and Respiratory DiseasesM S Leduc - Baylor College of MedicineY Yang - National Center for Immunization and Respiratory DiseasesC M Eng - Baylor GeneticsA Patel - Baylor GeneticsO K Rodningen - Oslo University HospitalD M Muzny - Baylor College of MedicineR A Gibbs - Baylor GeneticsI M Campbell - Baylor College of MedicineC A Shaw - Baylor GeneticsM W Baker - University of Wisconsin–MadisonV Zhang - Baylor College of MedicineJ R Lupski - Baylor GeneticsJ S Orange - Texas Children's HospitalF O Seeborg - Texas Children's HospitalA Stray-Pedersen - Oslo University Hospital
- Resource Type
- Journal article
- Publication Details
- Clinical and experimental immunology, Vol.178(3), pp.459-469
- Publisher
- Blackwell Science Inc
- DOI
- 10.1111/cei.12421
- PMID
- 25046553
- PMCID
- PMC4238873
- ISSN
- 0009-9104
- eISSN
- 1365-2249
- Language
- English
- Date published
- 12/2014
- Academic Unit
- Stead Family Department of Pediatrics; Rheumatology, Allergy, and Immunology; Internal Medicine
- Record Identifier
- 9984695829202771
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