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

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...

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Bibliographic Details
Published in:Human genetics 1998-07, Vol.103 (1), p.81-85
Main Authors: SASAKI, Y, ISEKI, M, YAMAGUCHI, S, KUROSAWA, Y, YAMAMOTO, T, MORIWAKI, Y, KENRI, T, SASAKI, T, YAMASHITA, R
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Arginine
Base Sequence
Biological and medical sciences
Child, Preschool
Chromosome Mapping
Chromosomes, Human, Pair 14
Codon, Terminator - genetics
Consanguinity
DNA Primers
Erythrocytes - enzymology
Exons
Female
Genes, Recessive
Genetic Carrier Screening
Glycine
Histidine
Humans
Immunodeficiencies
Immunodeficiencies. Immunoglobulinopathies
Immunopathology
Male
Medical sciences
Nuclear Family
Pedigree
Point Mutation
Polymerase Chain Reaction
Purine-Nucleoside Phosphorylase - deficiency
Purine-Nucleoside Phosphorylase - genetics
Serine
Severe Combined Immunodeficiency - enzymology
Severe Combined Immunodeficiency - genetics
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Summary: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.
ISSN:0340-6717
1432-1203
DOI:10.1007/s004390050787