Molecular genetics of peroxidase deficiency.

Myeloperoxidase (MPO) belongs to a family of related proteins which also includes eosinophil, thyroid, and lactoperoxidase. The MPO gene is a 14-kb gene located on the long arm of chromosome 17. Thus far four mutations (R569W, Y173C, M251T and a 14-base deletion in exon 9) have been identified in patients with MPO deficiency. As in other genetically determined diseases, many more mutations will eventually be revealed that cause this disease. Present evidence shows that most patients are compound heterozygotes, i.e., they have inherited different mutations on their paternal and maternal MPO alleles. Understanding why some patients with this genetic deficiency develop clinical symptoms while others do not requires mutation analyses of a large number of patients. This includes the analysis of genotype-phenotype relationships. Genotyping has also been started in patients with EPO-deficiency.