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.

[severe combined immunodeficiency]

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 CD 4 lymphocytopenia , the presence of CD 8 (+) 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 IL 7 R 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 )-7 R Î± 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 .

Diseases
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Diseases presenting "type allele" symptom

cowden syndrome

erythropoietic protoporphyria

fabry disease

junctional epidermolysis bullosa

severe combined immunodeficiency

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