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.
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.
Vettore
Silvia
S
Department of Medical and Surgical Sciences, University of Padova, Padova, Italy.
De Rocco
Daniela
D
Gerber
Bernhard
B
Scandellari
Raffaella
R
Bianco
Anna Monica
AM
Balduini
Carlo L
CL
Pecci
Alessandro
A
Fabris
Fabrizio
F
Savoia
Anna
A
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
C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D009711:Nucleotides; D024507:Nonmuscle Myosin Type IIA; D018995:Myosin Heavy Chains