• Carlo Zaninetti, Daniela De Rocco, Tania Giangregorio, Valeria Bozzi, Judit Demeter, Pietro Leoni, Patrizia Noris, Samppa Ryhänen, Serena Barozzi, Alessandro Pecci, and Anna Savoia.
• Department of Internal Medicine, IRCCS Policlicnico San Matteo Foundation, University of Pavia, Pavia, Italy.
• Hamostaseologie. 2019 Feb 1; 39 (1): 87-94.

AbstractMYH9-related disease (MYH9-RD) is an autosomal-dominant thrombocytopenia caused by mutations in the gene for non-muscle myosin heavy chain IIA (NMMHC-IIA). Patients present congenital macrothrombocytopenia and inclusions of NMMHC-IIA in leukocytes, and have a variable risk of developing kidney damage, sensorineural deafness, presenile cataracts and/or liver enzymes abnormalities. The spectrum of mutations found in MYH9-RD patients is limited and the incidence and severity of the non-congenital features are predicted by the causative MYH9 variant. In particular, different alterations of the C-terminal tail domain of NMMHC-IIA associate with remarkably different disease evolution. We report four novel MYH9 mutations affecting the tail domain of NMMHC-IIA and responsible for MYH9-RD in four families. Two variants cause amino acid substitutions in the coiled-coil region of NMMHC-IIA, while the other two are a splicing variant and a single nucleotide deletion both resulting in frameshift alterations of the short non-helical tailpiece. Characterization of phenotypes of affected individuals shows that all of these novel variants are associated with a mild clinical evolution of the disease.Georg Thieme Verlag KG Stuttgart · New York.

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