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

• Published in: European journal of medical genetics 2010-09, Vol.53 (5), p.256-260
• Main Authors: Vettore, Silvia, De Rocco, Daniela, Gerber, Bernhard, Scandellari, Raffaella, Bianco, Anna Monica, Balduini, Carlo L, Pecci, Alessandro, Fabris, Fabrizio, Savoia, Anna
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Blood Platelets - metabolism; Blood Platelets - pathology; Computational Biology; Exons; Female; Humans; Inclusion Bodies - metabolism; Kidney Failure, Chronic - metabolism; Macrothrombocytopenia; Medical Education; Missense and splicing mutation; Molecular Motor Proteins - genetics; Mutation, Missense; MYH9 gene; MYH9-related disease; Myosin Heavy Chains - genetics; Neutrophil inclusion; Neutrophils - cytology; Neutrophils - metabolism; Nonmuscle Myosin Type IIA - genetics; Nonmuscle Myosin Type IIA - metabolism; Nucleotides - genetics; Nucleotides - metabolism; RNA Splicing; Thrombocytopenia - metabolism
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2010.06.010

Abstract 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.