title: Genetic studies on myeloperoxidase deficiency in Italy.
abstract: Hereditary myeloperoxidase (MPO) deficiency is the most common neutrophil biochemical defect characterized by the lack of peroxidase activity. In order to extend the epidemiological studies on hereditary MPO deficiency in Italy, approximately 40,000 individuals were analyzed and 7 partial and 8 total MPO deficient subjects were identified. The genetic characterization of the subjects showed the presence of 3 already-known mutations (c.752T>C, c.1705C>T and c.1566_1579del14) and 6 novel mutations: four missense mutations (c.995C>T, c.1112A>G, c.1715T>G and c.1927T>C), then a deletion of an adenine within exon 3 (c.325delA) and a mutation within the 3' splice site of intron 11 (c.2031-2A>C). The novel missense mutations cause the substitution of residues the p.A332V, p.D371G, p.L572W and p.W643R, respectively, and can cause potential structural changes. The c.325delA deletion causes a shift of the reading frame with the occurrence of a premature stop codon within the pro-peptide. An eukaryotic expression system was set up to investigate how the c.2031-2A>C mutation alters the MPO pre-mRNA splicing. The activation of a cryptic 3' splice site located 109nt upstream of the authentic 3' splice site was observed. The 109nt-insertion might cause the rapid degradation of the MPO mRNA or, alternatively, might lead to the generation of an abnormal MPO precursor lacking the enzymatic activity.
authors.affiliation: Department of Physiology and Pathology, University of Trieste, Trieste, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Marchetti
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Patriarca
authors.forename: G Pietro
authors.initials: GP
authors.lastname: Solero
authors.forename: Francisco E
authors.initials: FE
authors.lastname: Baralle
authors.forename: Maurizio
authors.initials: M
authors.lastname: Romano
mesh_terms: D002460:Cell Line; D005260:Female; D015870:Gene Expression; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D009154:Mutation; D009195:Peroxidase / Q000172:deficiency* / Q000235:genetics; D014162:Transfection
chemical_list: D009195:Peroxidase