Purine nucleoside phosphorylase deficiency: a new case report and identification of two novel mutations (Gly156A1a and Val217Ile), only one of which (Gly156A1a) is deleterious.
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.
Moallem
Hamid Jack
HJ
Departments of Pediatrics and Medicine, Division of Allergy-Immunology, SUNY Health Science Center at Brooklyn, Brooklyn, New York 10203, USA.
Taningo
Gladys
G
Jiang
C K
CK
Hirschhorn
Rochelle
R
Fikrig
Senih
S
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
D004247:DNA; D011683:Purine-Nucleoside Phosphorylase