Hereditary myeloperoxidase deficiency due to a missense mutation of arginine 569 to tryptophan.

摘要: Hereditary deficiency of myeloperoxidase (MPO) is a common disorder but its genetic basis unknown. We have reported that neutrophils from individuals with MPO lack enzymatic and immunochemical evidence for mature 90-kDa precursor protein. thus hypothesized hereditary reflects defect in processing mutated primary translation product. Genomic DNA's normal subjects digested BglII probed radiolabeled cDNA 2.6-kilobase (kb) band. Previously we described the presence an aberrant 2.1-kb fragment digests most either partial or complete deficiency. describe here responsible mutation. The substitution thymidine cytosine exon 10 at nucleotide 8,089 genomic sequence results generation recognition site not present normally converts 2.6-kb to associated At amino acid level this mutation would replace arginine codon 569 tryptophan. Six seven patients had One subject was homozygous whereas five others were heterozygous locus. seventh patient only completely deficient without Thus, least two mutations three genotypes can produce phenotype