title: Purine nucleoside phosphorylase deficiency: a new case report and identification of two novel mutations (Gly156A1a and Val217Ile), only one of which (Gly156A1a) is deleterious.
abstract: Purine nucleoside phosphorylase (PNP) deficiency results in an autosomal recessive immunodeficiency disease characterized by initial involvement of cellular immunity and neurological manifestations with subsequent abnormalities of humoral immunity. The initial presentation and clinical course has varied widely in the relatively few published cases. The molecular basis has been reported in only 10 patients, precluding evaluation of phenotype-genotype relationships. We now report clinical, immunologic, and molecular findings in a new case of relatively early onset that emphasizes hypotonia and developmental delay as early manifestations. The patient carried two novel missense mutations (Gly56A1a and Val217Ile) on the same allele in apparent homozygosity. Expression of each of the mutant enzymes in vitro demonstrated that the Gly156A1a mutation abolished enzyme activity while the Val217Ile mutation was without obvious effect and is therefore a normal variant. Such "normal" polymorphisms might be associated with a variable response to the immunosuppressive PNP inhibitors currently in clinical trials.
authors.affiliation: Departments of Pediatrics and Medicine, Division of Allergy-Immunology, SUNY Health Science Center at Brooklyn, Brooklyn, New York 10203, USA.
authors.forename: Hamid Jack
authors.initials: HJ
authors.lastname: Moallem
authors.forename: Gladys
authors.initials: G
authors.lastname: Taningo
authors.forename: C K
authors.initials: CK
authors.lastname: Jiang
authors.forename: Rochelle
authors.initials: R
authors.lastname: Hirschhorn
authors.forename: Senih
authors.initials: S
authors.lastname: Fikrig
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005183:Failure to Thrive / Q000235:genetics* / Q000276:immunology; D017809:Fatal Outcome; D005260:Female; D005808:Genes, Recessive / Q000276:immunology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D007223:Infant; D020125:Mutation, Missense; D009422:Nervous System Diseases / Q000235:genetics* / Q000276:immunology; D011683:Purine-Nucleoside Phosphorylase / Q000172:deficiency* / Q000235:genetics / Q000276:immunology
chemical_list: D004247:DNA; D011683:Purine-Nucleoside Phosphorylase