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Genotype-phenotype correlation in MYH9-related thrombocytopenia.

Publication ,  Journal Article
Dong, F; Li, S; Pujol-Moix, N; Luban, NLC; Shin, SW; Seo, JH; Ruiz-Saez, A; Demeter, J; Langdon, S; Kelley, MJ
Published in: Br J Haematol
August 2005

Mutation of the non-muscle myosin heavy chain type II-A results in MYH9-related hereditary macrothrombocytopenia (HMTC), including four autosomal dominant platelet disorders: May-Hegglin anomaly (MHA), Sebastian (SBS), Fechtner (FS) and Epstein (EPS) syndrome. Denaturing high-performance liquid chromatography (DHPLC) was optimised for rapid screening of the seven exons harbouring all but one of the previously reported mutations of MYH9. Individuals from 13 families with phenotypes suggestive of MYH9-related HMTC were screened for mutations by DHPLC followed by direct sequencing of samples with aberrant column retention time. Mutations were identified in all 13 families. Six distinct missense heterozygous mutations were found in 10 families, including six families with MHA or SBS (E1841K, D1424N), three families with FS (R702H, R1165C, and D1424Y), and one family with EPS (S96L). A truncating mutation (R1933X) was found in three MHA families. 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 is associated with nephropathy and/or hearing loss. Mutations of other regions have intermediate expression of non-haematological characteristics. Further study is required to confirm these associations and understand the molecular basis for this genotype-phenotype relationship.

Duke Scholars

Published In

Br J Haematol

DOI

ISSN

0007-1048

Publication Date

August 2005

Volume

130

Issue

4

Start / End Page

620 / 627

Location

England

Related Subject Headings

  • Thrombocytopenia
  • Phenotype
  • Myosin Heavy Chains
  • Mutation, Missense
  • Molecular Motor Proteins
  • Kidney Diseases
  • Immunology
  • Humans
  • Heterozygote
  • Hearing Loss
 

Citation

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ICMJE
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Dong, F., Li, S., Pujol-Moix, N., Luban, N. L. C., Shin, S. W., Seo, J. H., … Kelley, M. J. (2005). Genotype-phenotype correlation in MYH9-related thrombocytopenia. Br J Haematol, 130(4), 620–627. https://doi.org/10.1111/j.1365-2141.2005.05658.x
Dong, Fan, Sufeng Li, Núria Pujol-Moix, Naomi L. C. Luban, Sang Won Shin, Jae Hong Seo, Arlette Ruiz-Saez, Judit Demeter, Scott Langdon, and Michael J. Kelley. “Genotype-phenotype correlation in MYH9-related thrombocytopenia.Br J Haematol 130, no. 4 (August 2005): 620–27. https://doi.org/10.1111/j.1365-2141.2005.05658.x.
Dong F, Li S, Pujol-Moix N, Luban NLC, Shin SW, Seo JH, et al. Genotype-phenotype correlation in MYH9-related thrombocytopenia. Br J Haematol. 2005 Aug;130(4):620–7.
Dong, Fan, et al. “Genotype-phenotype correlation in MYH9-related thrombocytopenia.Br J Haematol, vol. 130, no. 4, Aug. 2005, pp. 620–27. Pubmed, doi:10.1111/j.1365-2141.2005.05658.x.
Dong F, Li S, Pujol-Moix N, Luban NLC, Shin SW, Seo JH, Ruiz-Saez A, Demeter J, Langdon S, Kelley MJ. Genotype-phenotype correlation in MYH9-related thrombocytopenia. Br J Haematol. 2005 Aug;130(4):620–627.
Journal cover image

Published In

Br J Haematol

DOI

ISSN

0007-1048

Publication Date

August 2005

Volume

130

Issue

4

Start / End Page

620 / 627

Location

England

Related Subject Headings

  • Thrombocytopenia
  • Phenotype
  • Myosin Heavy Chains
  • Mutation, Missense
  • Molecular Motor Proteins
  • Kidney Diseases
  • Immunology
  • Humans
  • Heterozygote
  • Hearing Loss