Jpn. J. Infect. Dis., 57, S10-S12, 2004
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Genetic Studies on Myeloperoxidase Deficiency in Italy
Caterina Marchetti1,2, Pierluigi Patriarca1, G. Pietro Solero1, Francisco E. Baralle2 and Maurizio Romano1,2*
1Department of Physiology and Pathology, University of Trieste and 2International Centre for Genetic Engineering and Biotechnology, Trieste, Italy
SUMMARY: 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.