title: Direct evidence of autosomal recessive inheritance of Arg24 to termination codon in purine nucleoside phosphorylase gene in a family with a severe combined immunodeficiency patient.
abstract: Purine nucleoside phosphorylase (PNP) deficiency is a rare immunodeficiency disease involving a T-lymphocyte-dysfunction that is fatal unless bone marrow transplantation is successful. In this study we undertook genetic analysis of a patient with PNP deficiency. Sequencing of the PNP gene, which is located on chromosome 14ql3, of the patient led to the identification of three point mutations in exon 2 at amino acid positions 20 (His, silent mutation), 24 (Arg-->termination codon) and 51 (Ser-->Gly). Intrafamilial sequence analysis of exon 2 revealed that both parents were heterozygous for the Arg24 and termination codon 24 alleles. Two of their three children had inherited different homozygous alleles, termination codon 24 for the patient, and Arg24 for his healthy sibling. Transcriptional termination was suggested as the mechanism giving rise to the disorder in this case. A lack of PNP protein was also confirmed by immunoblot analysis of the patient's hemolysate. This could be the first report providing evidence of autosomal recessive inheritance in PNP deficiency by sequence-based analysis.
authors.affiliation: Department of Safety Research on Biologics, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan. yuko@nih.go.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: M
authors.initials: M
authors.lastname: Iseki
authors.forename: S
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Kurosawa
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Moriwaki
authors.forename: T
authors.initials: T
authors.lastname: Kenri
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
authors.forename: R
authors.initials: R
authors.lastname: Yamashita
mesh_terms: D000595:Amino Acid Sequence; D001120:Arginine; D001483:Base Sequence; D002675:Child, Preschool; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D018388:Codon, Terminator / Q000235:genetics; D003241:Consanguinity; D017931:DNA Primers; D004912:Erythrocytes / Q000201:enzymology; D005091:Exons; D005260:Female; D005808:Genes, Recessive; D006580:Genetic Carrier Screening; D005998:Glycine; D006639:Histidine; D006801:Humans; D008297:Male; D009679:Nuclear Family; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011683:Purine-Nucleoside Phosphorylase / Q000172:deficiency / Q000235:genetics*; D012694:Serine; D016511:Severe Combined Immunodeficiency / Q000201:enzymology* / Q000235:genetics*
chemical_list: D018388:Codon, Terminator; D017931:DNA Primers; D012694:Serine; D006639:Histidine; D001120:Arginine; D011683:Purine-Nucleoside Phosphorylase; D005998:Glycine