title: Two novel mutations in a purine nucleoside phosphorylase (PNP)-deficient patient.
abstract: 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.
authors.affiliation: Division of Immunology and Allergy, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Dalal
authors.forename: E
authors.initials: E
authors.lastname: Grunebaum
authors.forename: A
authors.initials: A
authors.lastname: Cohen
authors.forename: C M
authors.initials: CM
authors.lastname: Roifman
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002675:Child, Preschool; D018076:DNA, Complementary; D005091:Exons; D005260:Female; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D017354:Point Mutation; D011683:Purine-Nucleoside Phosphorylase / Q000172:deficiency / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000201:enzymology* / Q000235:genetics / Q000276:immunology
chemical_list: D018076:DNA, Complementary; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011683:Purine-Nucleoside Phosphorylase