Asp1424Asn MYH9 mutation results in an unstable protein responsible for the phenotypes in May-Hegglin anomaly/Fechtner syndrome

Samuel Deutsch, Alexandra Rideau, Marie Luce Bochaton-Piallat, Giuseppe Merla, Antoine Geinoz, Giulio Gabbiani, Torsten Schwede, Thomas Matthes, Stylianos E. Antonarakis, Photis Beris

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

May-Hegglin anomaly (MHA), Fechtner syndrome (FTNS), Sebastian syndrome (SBS), and Epstein syndrome (EPS) are a group of rare, autosomal dominant disorders characterized by thrombocytopenia, giant platelets, and Döhle-like inclusion bodies, together with variable manifestations of Alport-like symptoms that include high-tone sensorineural deafness, cataracts, and nephritis. These disorders result from mutations in the MYH9 gene, which encodes for the nonmuscle myosin heavy chain A protein (also known as NMMHC-A). To date 20 different mutations have been characterized for this gene, but no clear phenotype-genotype correlation has been established, and very little is known regarding the molecular pathogenesis of this group of diseases. Here, we describe 2 new families with MHA/FTNS phenotypes that have been characterized in terms of their mutations, protein localization in megakaryocytes, protein expression, and mRNA stability. Our findings suggest that, at least for the Asp1424Asn mutation in the MYH9 gene, the phenotypes result from a highly unstable protein. No abnormalities in protein localization or mRNA stability were observed. We hypothesize that haploinsufficiency of the MYH9 results in a failure to properly reorganize the cytoskeleton in megakaryocytes as required for efficient platelet production.

Original languageEnglish
Pages (from-to)529-534
Number of pages6
JournalBlood
Volume102
Issue number2
DOIs
Publication statusPublished - Jul 15 2003

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Phenotype
Mutation
Genes
Platelets
Proteins
Megakaryocytes
Protein Stability
RNA Stability
Blood Platelets
Messenger RNA
Myosin Heavy Chains
Haploinsufficiency
Nephritis
Inclusion Bodies
Genetic Association Studies
Deafness
Cytoskeleton
Thrombocytopenia
Cataract
MYH9-Related Disorders

ASJC Scopus subject areas

  • Hematology

Cite this

Asp1424Asn MYH9 mutation results in an unstable protein responsible for the phenotypes in May-Hegglin anomaly/Fechtner syndrome. / Deutsch, Samuel; Rideau, Alexandra; Bochaton-Piallat, Marie Luce; Merla, Giuseppe; Geinoz, Antoine; Gabbiani, Giulio; Schwede, Torsten; Matthes, Thomas; Antonarakis, Stylianos E.; Beris, Photis.

In: Blood, Vol. 102, No. 2, 15.07.2003, p. 529-534.

Research output: Contribution to journalArticle

Deutsch, S, Rideau, A, Bochaton-Piallat, ML, Merla, G, Geinoz, A, Gabbiani, G, Schwede, T, Matthes, T, Antonarakis, SE & Beris, P 2003, 'Asp1424Asn MYH9 mutation results in an unstable protein responsible for the phenotypes in May-Hegglin anomaly/Fechtner syndrome', Blood, vol. 102, no. 2, pp. 529-534. https://doi.org/10.1182/blood-2002-09-2783
Deutsch, Samuel ; Rideau, Alexandra ; Bochaton-Piallat, Marie Luce ; Merla, Giuseppe ; Geinoz, Antoine ; Gabbiani, Giulio ; Schwede, Torsten ; Matthes, Thomas ; Antonarakis, Stylianos E. ; Beris, Photis. / Asp1424Asn MYH9 mutation results in an unstable protein responsible for the phenotypes in May-Hegglin anomaly/Fechtner syndrome. In: Blood. 2003 ; Vol. 102, No. 2. pp. 529-534.
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