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.
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Authors | Carlo Zaninetti, Daniela De Rocco, Tania Giangregorio, Valeria Bozzi, Judit Demeter, Pietro Leoni, Patrizia Noris, Samppa Ryhänen, Serena Barozzi, Alessandro Pecci, Anna Savoia |
Journal | Hamostaseologie
(Hamostaseologie)
Vol. 39
Issue 1
Pg. 87-94
(Feb 2019)
ISSN: 2567-5761 [Electronic] Germany |
PMID | 29996171
(Publication Type: Journal Article)
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Copyright | Georg Thieme Verlag KG Stuttgart · New York. |
Chemical References |
- MYH9 protein, human
- Molecular Motor Proteins
- Protein Isoforms
- Myosin Heavy Chains
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Topics |
- 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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