MYH9-Related Thrombocytopenia: Four Novel Variants Affecting the Tail Domain of the Non-Muscle Myosin Heavy Chain IIA Associated with a Mild Clinical Evolution of the Disorder

Carlo Zaninetti, Daniela De Rocco, Tania Giangregorio, Valeria Bozzi, Judit Demeter, Pietro Leoni, Patrizia Noris, Samppa Ryhänen, Serena Barozzi, Alessandro Pecci, Anna Savoia

Research output: Contribution to journalArticle

Abstract

MYH9-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.
Original languageEnglish
Pages (from-to)87-94
Number of pages8
JournalHamostaseologie
Volume39
Issue number1
DOIs
Publication statusPublished - Feb 2019

Keywords

  • Adolescent
  • Adult
  • Aged
  • Amino Acid Substitution
  • Chromosome Breakage
  • Chromosome Disorders/*genetics/pathology
  • Female
  • Frameshift Mutation
  • Humans
  • Male
  • Middle Aged
  • Molecular Motor Proteins/chemistry/*genetics
  • *Mutation
  • Myosin Heavy Chains/chemistry/*genetics
  • Pedigree
  • Phenotype
  • Protein Domains
  • Protein Isoforms/chemistry/genetics
  • Thrombocytopenia/*congenital/genetics/pathology
  • Young Adult

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