Macrothrombocytopenia With Congenital Bilateral Cataracts: A Phenotype of MYH9 Disorder With Exon 24 Indel Mutations

Aoki, Takahiro; Kunishima, Shinji; Yamashita, Yoshiharu; Minamitani, Kanshi; Ota, Setsuo

doi:10.1097/mph.0000000000000998

Cited by 12 publications

(4 citation statements)

References 12 publications

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“…Mutations on MYH9 may cause MYH9 disorder, which is characterized by congenital macrothrombocytopenia complicated with young-adult-onset sensorineural hearing loss, nephropathy and congenital cataract. However, the etiologies of the diseases above are still unknown [21]. So far, there have been several reports of mutations in MYH9 gene ( Table 3).…”

Section: Discussionmentioning

confidence: 99%

Novel mutations associated with autosomal dominant congenital cataract are identified in Chinese families

Wang

Huang

Sun

et al. 2018

Preprint

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PurposeAs the leading cause of the impairment of vision of children, congenital cataract is considered as a hereditary disease, especially autosomal dominant congenital cataract (ADCC). The purpose of this study is to identify the genetic defect of six Chinese families with ADCC. Subjects and MethodsSix Chinese families with ADCC were recruited in the study. (103 members in total, 96 members alive, 27 patients in total) Genomic DNA samples extracting from probands' peripheral blood cells were captured the mutations using a specific eye disease enrichment panel with next generation sequencing. After initial pathogenicity prediction, sites with specific pathogenicity were screened for further validation. Sanger sequencing was conducted in the other individuals in the families and other 100 normal controls. Mutations definitely related with ADCC will then be analyzed by bioinformatics analysis. The pathogenic effect of the amino acid changes and structural and functional changes of the proteins were finally analyzed by bioinformatics analysis.

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Section: Discussionmentioning

confidence: 99%

Novel mutations associated with autosomal dominant congenital cataract are identified in Chinese families

Wang

Huang

Sun

et al. 2018

Preprint

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“…Early-onset cataracts are the rarest feature of MYH9-RD patients [41]. As such, the correlation between the precise mutation and the appearance of this manifestation is currently unknown, likely due to its low prevalence.…”

Section: Presenile Cataractsmentioning

confidence: 99%

Linking the Landscape of MYH9-Related Diseases to the Molecular Mechanisms that Control Non-Muscle Myosin II-A Function in Cells

Asensio-Juárez

Llorente-González

Vicente‐Manzanares

2020

Cells

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The MYH9 gene encodes the heavy chain (MHCII) of non-muscle myosin II A (NMII-A). This is an actin-binding molecular motor essential for development that participates in many crucial cellular processes such as adhesion, cell migration, cytokinesis and polarization, maintenance of cell shape and signal transduction. Several types of mutations in the MYH9 gene cause an array of autosomal dominant disorders, globally known as MYH9-related diseases (MYH9-RD). These include May-Hegglin anomaly (MHA), Epstein syndrome (EPS), Fechtner syndrome (FTS) and Sebastian platelet syndrome (SPS). Although caused by different MYH9 mutations, all patients present macrothrombocytopenia, but may later display other pathologies, including loss of hearing, renal failure and presenile cataracts. The correlation between the molecular and cellular effects of the different mutations and clinical presentation are beginning to be established. In this review, we correlate the defects that MYH9 mutations cause at a molecular and cellular level (for example, deficient filament formation, altered ATPase activity or actin-binding) with the clinical presentation of the syndromes in human patients. We address why these syndromes are tissue restricted, and the existence of possible compensatory mechanisms, including residual activity of mutant NMII-A and/or the formation of heteropolymers or co-polymers with other NMII isoforms.

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“…Cataracts or hearing disabilities often appear later than thrombocytosis or macrothrombocytosis because of the substitutional function of NMMHC-IIB or C. Our patient was screened for cataracts or hearing disability, but glomerulonephritis was the only sign at diagnosis. 6,19 The results of the renal biopsy indicated FSGS 15…”

Section: Discussionmentioning

confidence: 99%

Renal Biopsy-induced Hematoma and Infection in a Patient with Asymptomatic May-Hegglin Anomaly

et al. 2021

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The May-Hegglin anomaly is characterized by inherited thrombocytopenia, giant platelets, and leukocyte cytoplasmic inclusion bodies. The Fechtner, Sebastian, and Epstein syndromes are associated with mutations of the MYH9-coding nonmuscle myosin heavy chain ⅡA, similar to the May-Hegglin anomaly, and are together classified as MYH9 disorders. MYH9 disorders may include symptoms of Alport syndrome, including nephritis and auditory and ocular disorders. A 6-year-old boy was diagnosed with an MYH9 disorder after incidental discovery of hematuria and proteinuria. Focal segmental glomerulosclerosis was detected on renal biopsy. However, despite no prior bleeding diatheses, he developed a large post-biopsy hematoma despite a preprocedural platelet transfusion calculated to increase the platelet count from 54,000/µL to >150,000/µL. Idiopathic thrombocytopenic purpura is a major cause of pediatric thrombocytopenia following acute infection or vaccination, and patients with MYH9 disorders may be misdiagnosed with idiopathic thrombocytopenic purpura and inappropriately treated with corticosteroids. Careful differential diagnosis is important in thrombocytopenic patients with hematuria and proteinuria for the early detection of thrombocytopenia. Patients with MYH9 disorders require close follow-up and treatment with angiotensin Ⅱ receptor blockers to prevent the onset of progressive nephritis, which may necessitate hemodialysis or renal transplantation. The need for renal biopsy in patients with MYH9 disorders should be carefully considered because there could be adverse outcomes even after platelet transfusion.

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Macrothrombocytopenia With Congenital Bilateral Cataracts: A Phenotype of MYH9 Disorder With Exon 24 Indel Mutations

Cited by 12 publications

References 12 publications

Novel mutations associated with autosomal dominant congenital cataract are identified in Chinese families

Novel mutations associated with autosomal dominant congenital cataract are identified in Chinese families

Linking the Landscape of MYH9-Related Diseases to the Molecular Mechanisms that Control Non-Muscle Myosin II-A Function in Cells

Renal Biopsy-induced Hematoma and Infection in a Patient with Asymptomatic May-Hegglin Anomaly

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