Position of nonmuscle myosin heavy chain IIA (NMMHC‐IIA) mutations predicts the natural history of MYH9‐related disease

@article{Pecci2008PositionON,
  title={Position of nonmuscle myosin heavy chain IIA (NMMHC‐IIA) mutations predicts the natural history of MYH9‐related disease},
  author={Alessandro Pecci and Emanuele Panza and N{\'u}ria Pujol-Moix and Catherine Klersy and Filomena di Bari and Valeria Bozzi and Paolo Gresele and Stefan Lethagen and Fabrizio Fabris and Carlo Dufour and Antonio Granata and Michael Doubek and Carmine Pecoraro and Pasi A. Koivisto and Paula G. Heller and Achille Iolascon and Patrizia Alvisi and Dirk Schwabe and Erica De Candia and Bianca Rocca and Umberto Russo and Ugo Ramenghi and Patrizia Noris and Marco Seri and Carlo L. Balduini and Anna Savoia},
  journal={Human Mutation},
  year={2008},
  volume={29}
}
MYH9‐related disease (MYH9‐RD) is a rare autosomal‐dominant disorder caused by mutations in MYH9, the gene for the heavy chain of nonmuscle myosin IIA (NMMHC‐IIA). All patients present from birth with macrothrombocytopenia, but in infancy or adult life, some of them develop sensorineural deafness, presenile cataracts, and/or progressive nephritis leading to end‐stage renal failure. No consistent correlations have been identified between the 27 different MYH9 mutations identified so far and the… Expand
Nonmuscle Myosin Heavy Chain IIA Mutation Predicts Severity and Progression of Sensorineural Hearing Loss in Patients With MYH9-Related Disease
TLDR
Investigation of the severity and propensity for progression of SNHL in a large series of MYH9-RD patients in relation to the causative NMMHC-IIA mutations provided useful tools to predict the progression and the expected degree of severity ofSNHL in individual MYH 9- RD patients. Expand
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.
TLDR
Characterization of phenotypes of affected individuals shows that all of the novel MYH9 mutations affecting the tail domain of NMMHC-IIA are associated with a mild clinical evolution of the disease. Expand
MYH9 related disease: four novel mutations of the tail domain of myosin‐9 correlating with a mild clinical phenotype
TLDR
Four families are reported, each with a novel mutation: two missense mutations, in exons 31 and 32, and two out of frame deletions in exon 40, confirming that alterations of the tail domain cause a mild form of MYH9‐RD with no clinically relevant defects. Expand
Heavy chain myosin 9-related disease (MYH9 -RD): neutrophil inclusions of myosin-9 as a pathognomonic sign of the disorder.
TLDR
It is demonstrated that the myosin-9 inclusions in neutrophils are a pathognomonic sign of the disease, demonstrating that the identification of the specific MYH9 mutation is still of importance for prognostic aspects of MyH9-RD. Expand
MYH9-related disease: Five novel mutations expanding the spectrum of causative mutations and confirming genotype/phenotype correlations
TLDR
Five families of children with congenital macrothrombocytopenia and typical inclusion bodies in neutrophils associated with a variable risk of developing sensorineural deafness, presenile cataract, and/or progressive nephropathy are reported. Expand
MYH9-related platelet disorders.
TLDR
A short history of MYH9-related disorders is provided, the clinical and laboratory characteristics, a diagnostic algorithm is described, recent results of animal models, and aspects of therapeutic management are discussed. Expand
MYH9‐Related Disease: A Novel Prognostic Model to Predict the Clinical Evolution of the Disease Based on Genotype–Phenotype Correlations
TLDR
Findings in genotype–phenotype correlations are essential to patients' clinical management and genetic counseling and are discussed in view of molecular pathogenesis of MYH9‐RD. Expand
MYH9-related disease: Report on five German families and description of a novel mutation
TLDR
The MYH9 gene was analyzed in five German families with suspectedMYH9RD because of the presence of myosin-9 aggregates in neutrophils and all nonsense or frameshift mutations reported so far for patients with MYH 9RD are located in this region and are predicted to have a good prognosis concerning the risk of non-hematologic manifestations. Expand
Identification of the first duplication in MYH9-related disease: a hot spot for unequal crossing-over within exon 24 of the MYH9 gene.
TLDR
A family with three affected members carrying a novel mutation, the first duplication or the deletion in exon 24 were affected with bilateral neonatal cataracts, and it is speculated that these mutations might correlate with the ocular defect, reported only in 16% of MYH9RD patients. Expand
Advances in the understanding of MYH9 disorders
TLDR
The present review summarizes the recent advances in genetic diagnosis and the understanding of the pathogenetic mechanisms of MYH9 mutations and the development of nonhematological complications and recommends prophylactic treatment. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 39 REFERENCES
Nonmuscle myosin heavy chain IIA mutations define a spectrum of autosomal dominant macrothrombocytopenias: May-Hegglin anomaly and Fechtner, Sebastian, Epstein, and Alport-like syndromes.
TLDR
The data suggest that MHA, SBS, FTNS, EPS, and APSM comprise a phenotypic spectrum of disorders, all caused by MYH9 mutations, and the name "MYHIIA syndrome" is proposed to encompass all of these disorders. Expand
Expression of the nonmuscle myosin heavy chain IIA in the human kidney and screening for MYH9 mutations in Epstein and Fechtner syndromes.
TLDR
The expression of MYH9 in the fetal and mature human kidney was studied, and the 40 coding exons of the gene were screened by single-strand conformation polymorphism in 12 families presenting with the association of MTCP and nephropathy. Expand
Mutations in Human Nonmuscle Myosin IIA Found in Patients with May-Hegglin Anomaly and Fechtner Syndrome Result in Impaired Enzymatic Function*
TLDR
Two of the recently described mutations, N93K and R702C, are conserved in smooth and nonmuscle myosins from vertebrates and lie in the head domain of myosin, Interestingly, the two mutations lie within close proximity in the three-dimensional structure of myOSin. Expand
Mutation of MYH9, encoding non-muscle myosin heavy chain A, in May-Hegglin anomaly
TLDR
The identification of MYH9 as the disease gene for MHA establishes the pathogenesis of the disorder, should provide further insight into the processes of normal platelet formation and may facilitate identification of the genetic basis of related disorders. Expand
Pathogenetic mechanisms of hematological abnormalities of patients with MYH9 mutations.
TLDR
Results indicate that haploinsufficiency of NMMHC-IIA in megakaryocytic lineage is the mechanism of macrothrombocytopenia consequent to MYH9 mutations, whereas in granulocytes a dominant-negative effect of mutant allele is involved in the formation of inclusion bodies. Expand
Genotype–phenotype correlation in MYH9‐related thrombocytopenia
TLDR
A review of all published mutations suggests that mutation in the C‐terminal coiled coil region or truncation of the tailpiece is associated with haematological‐only phenotype, while mutation of the head ATPase domain frequently isassociated with nephropathy and/or hearing loss. Expand
Immunofluorescence Analysis of Neutrophil Nonmuscle Myosin Heavy Chain-A in MYH9 Disorders: Association of Subcellular Localization with MYH9 Mutations
TLDR
Immunofluorescence analysis of neutrophil NMMHCA is useful as a screening test for the clear hematopathologic classification of MYH9 disorders and it is proposed that the localization pattern can be classified into three groups according to the number, size, and shape of the fluorescence-labeled NMMhCA granule. Expand
Rod mutations associated with MYH9-related disorders disrupt nonmuscle myosin-IIA assembly.
TLDR
It is demonstrated that the most common mutations in MYH9, lesions in the rod, cause defects in nonmuscle myosin-IIA assembly, and the application of these methods to biochemically characterize rod mutations could be extended to other myosins responsible for disease. Expand
MYH9-Related Disease: May-Hegglin Anomaly, Sebastian Syndrome, Fechtner Syndrome, and Epstein Syndrome Are not Distinct Entities but Represent a Variable Expression of a Single Illness
TLDR
The term “MHY9-related disease,” which better interprets the recent knowledge in this field and identifies all patients at risk of developing renal, hearing, or visual defects, is proposed. Expand
Identification of six novel MYH9 mutations and genotype-phenotype relationships in autosomal dominant macrothrombocytopenia with leukocyte inclusions
TLDR
MHA, SBS, and FTNS appear to represent a class of allelic disorders with variable phenotypic diversity with clear phenotype–genotype relationships, according to three previous reports, including the authors'. Expand
...
1
2
3
4
...