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

Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recess ive disease, which presents clinically as severe combined immunodeficiency (SCID). We report here two novel mutations in the PNP gene that result in S CID 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 aci d 57. The paternal-derived mutation is a G to A transition at position +1 i n 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 abe rrantly spliced mRNA terminates prematurely after only 89 amino acids. Both mutations predict severely truncated proteins resulting in a complete defi ciency of PNP enzymatic activity, yet the development of profound immunodef iciency in this patient is greatly delayed.