@article {3635,
	title = {MYH9-related disease: a novel prognostic model to predict the clinical evolution of the disease based on genotype-phenotype correlations.},
	journal = {Hum Mutat},
	volume = {35},
	year = {2014},
	month = {2014 Feb},
	pages = {236-47},
	abstract = {<p>MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in the gene for nonmuscle myosin heavy chain IIA (NMMHC-IIA). MYH9-RD is characterized by a considerable variability in clinical evolution: patients present at birth with only thrombocytopenia, but some of them subsequently develop sensorineural deafness, cataract, and/or nephropathy often leading to end-stage renal disease (ESRD). We searched for genotype-phenotype correlations in the largest series of consecutive MYH9-RD patients collected so far (255 cases from 121 families). Association of genotypes with noncongenital features was assessed by a generalized linear regression model. The analysis defined disease evolution associated to seven different MYH9 genotypes that are responsible for 85\% of MYH9-RD cases. Mutations hitting residue R702 demonstrated a complete penetrance for early-onset ESRD and deafness. The p.D1424H substitution associated with high risk of developing all the noncongenital manifestations of disease. Mutations hitting a distinct hydrophobic seam in the NMMHC-IIA head domain or substitutions at R1165 associated with high risk of deafness but low risk of nephropathy or cataract. Patients with p.E1841K, p.D1424N, and C-terminal deletions had low risk of noncongenital defects. These findings are essential to patients{\textquoteright} clinical management and genetic counseling and are discussed in view of molecular pathogenesis of MYH9-RD.</p>},
	keywords = {Adult, Age of Onset, Amino Acid Substitution, Cataract, Female, Genetic Association Studies, Genotype, Hearing Loss, Sensorineural, Humans, Italy, Linear Models, Male, Molecular Motor Proteins, Mutation, Myosin Heavy Chains, Phenotype, Risk Factors, Thrombocytopenia},
	issn = {1098-1004},
	doi = {10.1002/humu.22476},
	author = {Pecci, Alessandro and Klersy, Catherine and Gresele, Paolo and Lee, Kieran J D and De Rocco, Daniela and Bozzi, Valeria and Russo, Giovanna and Heller, Paula G and Loffredo, Giuseppe and Ballmaier, Matthias and Fabris, Fabrizio and Beggiato, Eloise and Kahr, Walter H A and Pujol-Moix, N{\'u}ria and Platokouki, Helen and Van Geet, Christel and Noris, Patrizia and Yerram, Preethi and Hermans, Cedric and Gerber, Bernhard and Economou, Marina and De Groot, Marco and Zieger, Barbara and De Candia, Erica and Fraticelli, Vincenzo and Kersseboom, Rogier and Piccoli, Giorgina B and Zimmermann, Stefanie and Fierro, Tiziana and Glembotsky, Ana C and Vianello, Fabrizio and Zaninetti, Carlo and Nicchia, Elena and G{\"u}thner, Christiane and Baronci, Carlo and Seri, Marco and Knight, Peter J and Balduini, Carlo L and Savoia, Anna}
}
@article {1712,
	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.},
	journal = {Eur J Med Genet},
	volume = {53},
	year = {2010},
	month = {2010 Sep-Oct},
	pages = {256-60},
	abstract = {<p>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{\textquoteright}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.</p>},
	keywords = {Adolescent, Adult, Blood Platelets, Computational Biology, Exons, Female, Humans, Inclusion Bodies, Kidney Failure, Chronic, Molecular Motor Proteins, Mutation, Missense, Myosin Heavy Chains, Neutrophils, Nonmuscle Myosin Type IIA, Nucleotides, RNA Splicing, Thrombocytopenia},
	issn = {1878-0849},
	doi = {10.1016/j.ejmg.2010.06.010},
	author = {Vettore, Silvia and De Rocco, Daniela and Gerber, Bernhard and Scandellari, Raffaella and Bianco, Anna Monica and Balduini, Carlo L and Pecci, Alessandro and Fabris, Fabrizio and Savoia, Anna}
}
