Two novel mutations in a purine nucleoside phosphorylase (PNP)-deficient patient


Corresponding author: Dr Chaim M Roifman, Division of Immunology/Allergy, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada. Tel: +1 416 8138623/8629; fax: +1 416 8138624; e-mail:


Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive disease, which presents clinically as severe combined immunodeficiency (SCID). We report here two novel mutations in the PNP gene that result in SCID phenotype, in a single patient. The maternal-derived allele carries a C to T transition in exon 2 resulting in a premature stop codon at amino acid 57. The paternal-derived mutation is a G to A transition at position +1 in intron 3, causing a complete skipping of exon 3 and a reading frameshift at the exon 2–exon 4 junction. The predicted polypeptide encoded by the aberrantly spliced mRNA terminates prematurely after only 89 amino acids. Both mutations predict severely truncated proteins resulting in a complete deficiency of PNP enzymatic activity, yet the development of profound immunodeficiency in this patient is greatly delayed.