A MARKED DECREASE IN DEFENSIN MESSENGER-RNA IN THE ONLY CASE OF CONGENITAL NEUTROPHIL-SPECIFIC GRANULE DEFICIENCY REPORTED IN JAPAN

A deficiency of defensins (human neutrophil peptides, HNP) has been pr eviously demonstrated in two individuals with congenital neutrophil-sp ecific granule deficiency (SGD), but its genetic basis is not well und erstood. We have studied another case of SGD, the only case reported i n Japan, to elucidate the molecular basis of defensin deficiency. Usin g Western blot analysis, we showed for the first time that HNP-4, a no vel human defensin, was also deficient in the patient's neutrophils. N orthern blot analysis demonstrated that the defensin mRNA was absent i n the bone marrow cells of the patient. Limited Southern blot analysis , using a defensin cDNA probe, did not reveal any differences in fragm ent patterns of the genomic DNA between the patient and the control. W e propose that the defensin deficiency in our patient is a consequence of a marked decrease in defensin mRNA in neutrophil precursors. Our f indings were consistent with a previous speculation suggesting that th e SGD defect occurs at the level of transcription.