DIRECT EVIDENCE OF AUTOSOMAL RECESSIVE INHERITANCE OF ARG24 TO TERMINATION CODON IN PURINE NUCLEOSIDE PHOSPHORYLASE GENE IN A FAMILY WITH ASEVERE COMBINED IMMUNODEFICIENCY PATIENT

Purine nucleoside phosphorylase (PNP) deficiency is a rare immunodefic iency disease involving a T-lymphocyte-dysfunction that is fatal unles s bone marrow transplantation is successful. In this study we undertoo k genetic analysis of a patient with PNP deficiency. Sequencing of the PNP gene, which is located on chromosome 14q13, of the patient led to the identification of three point mutations in exon 2 at amino acid p ositions 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 codo n 24 alleles. Two of their three children had inherited different homo zygous alleles, termination codon 24 for the patient, and Arg24 for hi s healthy sibling. Transcriptional termination was suggested as the me chanism giving rise to the disorder in this case. A lack of PNP protei n was also confirmed by immunoblot analysis of the patient's hemolysat e. This could be the first report providing evidence of autosomal rece ssive inheritance in PNP deficiency by sequence-based analysis.