title: 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.
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.
authors.affiliation: Department of Medical and Surgical Sciences, University of Padova, Padova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vettore
authors.forename: Daniela
authors.initials: D
authors.lastname: De Rocco
authors.forename: Bernhard
authors.initials: B
authors.lastname: Gerber
authors.forename: Raffaella
authors.initials: R
authors.lastname: Scandellari
authors.forename: Anna Monica
authors.initials: AM
authors.lastname: Bianco
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Balduini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pecci
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Fabris
authors.forename: Anna
authors.initials: A
authors.lastname: Savoia
mesh_terms: D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D019295:Computational Biology; D005091:Exons; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism; D020409:Molecular Motor Proteins / Q000235:genetics*; D020125:Mutation, Missense; D018995:Myosin Heavy Chains / Q000235:genetics*; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D024507:Nonmuscle Myosin Type IIA / Q000235:genetics* / Q000378:metabolism; D009711:Nucleotides / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing; D013921:Thrombocytopenia / Q000378:metabolism
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D009711:Nucleotides; D024507:Nonmuscle Myosin Type IIA; D018995:Myosin Heavy Chains