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

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1 Citation (Scopus)

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
JournalHamostaseologie
DOIs
Publication statusAccepted/In press - Jul 11 2018

Fingerprint

Myosin Heavy Chains
Thrombocytopenia
Mutation
Deafness
Amino Acid Substitution
Cataract
Leukocytes
Nucleotides
Phenotype
Kidney
Liver
Incidence
Enzymes
Genes
MYH9-Related Disorders

Keywords

  • inherited platelet disorders
  • inherited thrombocytopenia
  • MYH9 -related disease
  • non-muscle myosin IIA

ASJC Scopus subject areas

  • Hematology

Cite this

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title = "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",
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.",
keywords = "inherited platelet disorders, inherited thrombocytopenia, MYH9 -related disease, non-muscle myosin IIA",
author = "Carlo Zaninetti and {de Rocco}, Daniela and Tania Giangregorio and Valeria Bozzi and Judit Demeter and Pietro Leoni and Patrizia Noris and Samppa Ryh{\"a}nen and Serena Barozzi and Alessandro Pecci and Anna Savoia",
year = "2018",
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doi = "10.1055/s-0038-1645840",
language = "English",
journal = "Hamostaseologie",
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T1 - MYH9 -Related Thrombocytopenia

T2 - Four Novel Variants Affecting the Tail Domain of the Non-Muscle Myosin Heavy Chain IIA Associated with a Mild Clinical Evolution of the Disorder

AU - Zaninetti, Carlo

AU - de Rocco, Daniela

AU - Giangregorio, Tania

AU - Bozzi, Valeria

AU - Demeter, Judit

AU - Leoni, Pietro

AU - Noris, Patrizia

AU - Ryhänen, Samppa

AU - Barozzi, Serena

AU - Pecci, Alessandro

AU - Savoia, Anna

PY - 2018/7/11

Y1 - 2018/7/11

N2 - 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.

AB - 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.

KW - inherited platelet disorders

KW - inherited thrombocytopenia

KW - MYH9 -related disease

KW - non-muscle myosin IIA

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