TY - JOUR T1 - A G to C transversion at the last nucleotide of exon 25 of the MYH9 gene results in a missense mutation rather than in a splicing defect. JF - Eur J Med Genet Y1 - 2010 A1 - Vettore, Silvia A1 - De Rocco, Daniela A1 - Gerber, Bernhard A1 - Scandellari, Raffaella A1 - Bianco, Anna Monica A1 - Balduini, Carlo L A1 - Pecci, Alessandro A1 - Fabris, Fabrizio A1 - Savoia, Anna KW - Adolescent KW - Adult KW - Blood Platelets KW - Computational Biology KW - Exons KW - Female KW - Humans KW - Inclusion Bodies KW - Kidney Failure, Chronic KW - Molecular Motor Proteins KW - Mutation, Missense KW - Myosin Heavy Chains KW - Neutrophils KW - Nonmuscle Myosin Type IIA KW - Nucleotides KW - RNA Splicing KW - Thrombocytopenia AB -

MYH9-related disease (MYH9-RD) is a rare autosomal dominant disorder caused by mutations in MYH9, the gene encoding the heavy chain of non-muscle myosin IIA. Patients present with congenital macrothrombocytopenia and inclusion bodies in neutrophils and might develop sensorineural deafness, presenile cataract, and/or progressive nephropathy leading to end-stage renal failure. In two families with macrothrombocytopenia we identified a novel c.3485G > C mutation in the last nucleotide of exon 25. Bioinformatic tools for splice site prediction and minigene functional test predicted splicing anomalies of exon 25. However, analysis of RNA purified from patient's peripheral blood did not allowed us to detect any anomalies, suggesting that RNA processing is correct at least in this tissue. Therefore, we concluded that c.3485G > C leads to a novel missense mutation (p.Arg1162Thr) of myosin-9, which resulted to be slightly degraded in patient platelets. A precise definition of the effect of mutations is fundamental to improve our knowledge into the pathogenetic mechanisms responsible for the disease.

VL - 53 IS - 5 U1 - http://www.ncbi.nlm.nih.gov/pubmed/20603234?dopt=Abstract ER -