Historical hematology: May–Hegglin anomaly

Saito, Hidehiko; Kunishima, Shinji

doi:10.1002/ajh.21102

Cited by 36 publications

(28 citation statements)

References 19 publications

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“…In contrast, chromosome 22 marker rs5769116 (62.92 cM, 45.44 Mb) revealed moderate evidence for both linkage (p = 0.0018, LOD = 1.83) and association (p = 0.0019) in EA (fig. 2g) some 10 Mb distal to MYH9/APOL1 – genes associated with several nondiabetic kidney diseases [9,18,19,20]. …”

Section: Resultsmentioning

confidence: 99%

Genomewide Linkage Scan for Diabetic Renal Failure and Albuminuria: The FIND Study

et al. 2011

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Background: Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in patients with type 1 and type 2 diabetes. The multicenter FIND consortium aims to identify genes for DN and its associated quantitative traits, e.g. the urine albumin:creatinine ratio (ACR). Herein, the results of whole-genome linkage analysis and a sparse association scan for ACR and a dichotomous DN phenotype are reported in diabetic individuals. Methods: A genomewide scan comprising more than 5,500 autosomal single nucleotide polymorphism markers (average spacing of 0.6 cM) was performed on 1,235 nuclear and extended pedigrees (3,972 diabetic participants) ascertained for DN from African-American (AA), American-Indian (AI), European-American (EA) and Mexican-American (MA) populations. Results: Strong evidence for linkage to DN was detected on chromosome 6p (p = 8.0 × 10^–5, LOD = 3.09) in EA families as well as suggestive evidence for linkage to chromosome 7p in AI families. Regions on chromosomes 3p in AA, 7q in EA, 16q in AA and 22q in MA displayed suggestive evidence of linkage for urine ACR. The linkage peak on chromosome 22q overlaps the MYH9/APOL1 gene region, previously implicated in AA diabetic and nondiabetic nephropathies. Conclusion: These results strengthen the evidence for previously identified genomic regions and implicate several novel loci potentially involved in the pathogenesis of DN.

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Section: Resultsmentioning

confidence: 99%

Genomewide Linkage Scan for Diabetic Renal Failure and Albuminuria: The FIND Study

et al. 2011

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“…MayHegglin anomaly and Sebastian syndrome are defined as macrothrombocytopenia and Döhle-like bodies without other organ involvement and these two diseases are differentiated by ultrastructural examination of leukocyte inclusions. Fechtner syndrome has the additional clinical features of glomerulopathy, sensorineural deafness, and cataracts, and Epstein syndrome differs from Fechtner syndrome in that it does not involve cataracts or Döhle-like bodies [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Renal manifestations of patients with MYH9-related disorders

et al. 2011

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MYH9-related disorders are a group of autosomal, dominantly inherited disorders caused by mutations of the MYH9 gene, which encodes the non-muscle myosin heavy chain IIA (NMMHC-IIA). May-Hegglin anomaly and Sebastian, Fechtner, and Epstein syndromes belong to this group. Macrothrombocytopenia is a common characteristic associated with MYH9-related disorders, and basophilic cytoplasmic inclusion bodies in leukocytes (Döhle-like bodies), deafness, cataracts, and glomerulopathy are also found in some patients. In this study, renal manifestations of 7 unrelated Korean patients with MYH9-related disorders were analyzed. Of a total of 7 patients, 4 had disease-related family histories. One familial case had a mutation in the tail domain of NMMHC-IIA and showed milder renal involvement with preserved renal function by his 30s. Among the 3 familial cases without renal involvement, 2 had mutations in the tail domain of NMMHC-IIA and 1 had a mutation in the motor domain. The remaining 3 sporadic cases had severe renal involvement with rapid progression to end-stage renal disease and mutations located in the motor domain. In summary, mutations in the motor domain of NMMHC-IIA and negative family history were associated with severe renal involvement in patients with MYH9-related disorders. These results are in agreement with those of previous reports.

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“…[1][2][3] These disorders are caused by heterozygous mutations in MYH9, which encodes nonmuscle myosin heavy chain-IIA (NMMHC-IIA), and include the May-Hegglin anomaly, Sebastian, Fechtner, and Epstein syndromes, Alport-like syndrome with macrothrombocytopenia, and nonsyndromic deafness (DFNA17). [4][5][6] An MYH9 mutation is always associated with macrothrombocytopenia and granulocyte inclusion bodies from birth, but it does not predict the development of Alport manifestations, including nephritis, deafness, and cataracts.…”

Section: Introductionmentioning

confidence: 99%

Differential expression of wild-type and mutant NMMHC-IIA polypeptides in blood cells suggests cell-specific regulation mechanisms in MYH9 disorders

Kunishima

Hamaguchi

Saito

2008

Blood

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MYH9 disorders such as May-Hegglin anomaly are characterized by macrothrombocytopenia and cytoplasmic granulocyte inclusion bodies that result from mutations in MYH9, the gene for nonmuscle myosin heavy chain-IIA (NMMHC-IIA). We examined the expression of mutant NMMHC-IIA polypeptide in peripheral blood cells from patients with MYH9 5770delG and 5818delG mutations. A specific antibody to mutant NMMHC-IIA (NT629) was raised against the abnormal carboxyl-terminal residues generated by 5818delG. NT629 reacted to recombinant 5818delG NMMHC-IIA but not to wild-type NMMHC-IIA, and did not recognize any cellular components of normal peripheral blood cells. Immunofluorescence and immunoblotting revealed that mutant NMMHC-IIA was present and sequestrated only in inclusion bodies within neutrophils, diffusely distributed throughout lymphocyte cytoplasm, sparsely localized on a diffuse cytoplasmic background in monocytes, and uniformly distributed at diminished levels only in large platelets. Mutant NMMHC-IIA did not translocate to lamellipodia in surface activated platelets. Wild-type NMMHC-IIA was homogeneously distributed among megakaryocytes derived from the peripheral blood CD34 ؉ cells of patients, but coarse mutant NMMHC-IIA was heterogeneously scattered without abnormal aggregates in the cytoplasm. We show the differential expression of mutant NMMHC IntroductionMYH9 disorders are autosomal dominant macrothrombocytopenias characterized by giant platelets, thrombocytopenia, and Döhle body-like inclusion bodies in the cytoplasm of granulocytes. [1][2][3] These disorders are caused by heterozygous mutations in MYH9, which encodes nonmuscle myosin heavy chain-IIA (NMMHC-IIA), and include the May-Hegglin anomaly, Sebastian, Fechtner, and Epstein syndromes, Alport-like syndrome with macrothrombocytopenia, and nonsyndromic deafness (DFNA17). [4][5][6] An MYH9 mutation is always associated with macrothrombocytopenia and granulocyte inclusion bodies from birth, but it does not predict the development of Alport manifestations, including nephritis, deafness, and cataracts. A mutation of MYH9 alone does not seem to cause associated Alport manifestations, and unknown genetic and/or epigenetic factors might influence the phenotypic consequences of MYH9 mutations. [7][8][9][10] Although the molecular mechanisms of hematologic abnormalities are under investigation, those of the kidney, cochlea, and lens are completely unknown.We previously showed that NMMHC-IIA polypeptide accumulates in neutrophil cytoplasm and forms inclusion bodies in patients with MYH9 disorders. The nature of the cytoplasmic accumulation can be classified according to the number, size, and shape of accumulated NMMHC-IIA granules, into types I, II, and III. Type I comprises 1 or 2 large (0.5-2 m), intensely stained, oval-to spindle-shaped cytoplasmic NMMHC-IIA-positive granules. Type II comprises up to 20 circular to oval cytoplasmic spots (Յ 1 m). Type III appears as speckled staining. Furthermore, the pattern of localization correlates with the site of MYH9 ...

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Historical hematology: May–Hegglin anomaly

Cited by 36 publications

References 19 publications

Genomewide Linkage Scan for Diabetic Renal Failure and Albuminuria: The FIND Study

Genomewide Linkage Scan for Diabetic Renal Failure and Albuminuria: The FIND Study

Renal manifestations of patients with MYH9-related disorders

Differential expression of wild-type and mutant NMMHC-IIA polypeptides in blood cells suggests cell-specific regulation mechanisms in MYH9 disorders

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