Purine nucleoside phosphorylase deficiency presenting as severe combined immune deficiency.
Purine nucleoside phosphorylase (PNP) deficiency is an autosomal recessive genetic disorder of the purine salvage pathway, associated with a variable extent of immunodeficiency. Here, we report a PNP-deficient patient who presented early in life with clinical and laboratory characteristics of severe combined immunodeficiency, including severe infections, marked T-and B-cell deficiency, lack of lymphocyte response to mitogenic stimulation, monoclonal T-cell receptors representation and the absence of T-cell receptor excision circles and Kappa-receptor excision circles. The patient carried homozygote mutation at the PNP gene that putatively led to aberrant splicing, allowing normal and abnormally spliced products from the mutant alleles. We suggest that the aberrant slice site was used preferentially over the normal slice site in some cells correlating with the severity of disease.
Cancer Research Center, Pediatric Department, Pediatric Immunology Service, Jeffery Modell Foundation (JMF) Center, Edmond and Lily Safra Children's Hospital, Tel Aviv University, Tel Aviv, Israel. rsomech@hotmail.com
Raz
R
Somech
Atar
A
Lev
Galia
G
Grisaru-Soen
Shelly I
SI
Shiran
Amos J
AJ
Simon
Eyal
E
Grunebaum
D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism; D002180:Candidiasis, Oral / Q000209:etiology; D003241:Consanguinity; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007223:Infant; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D009154:Mutation / Q000235:genetics; D014066:Palatine Tonsil / Q000276:immunology; D000081207:Primary Immunodeficiency Diseases; D019154:Protein Splicing / Q000235:genetics; D011683:Purine-Nucleoside Phosphorylase / Q000172:deficiency* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012128:Respiratory Distress Syndrome / Q000209:etiology; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D011948:Receptors, Antigen, T-Cell; D002097:C-Reactive Protein; D011683:Purine-Nucleoside Phosphorylase