Next-generation sequencing for the diagnosis of MYH9-RD: predicting pathogenic variants

Loredana Bury, Karyn Megy, Jonathan C Stephens, Luigi Grassi, Daniel Greene, Nick Gleadall, Karina Althaus, David Allsup, Tadbir Bariana, Mariana Bonduel, Nora Butta, Peter Collins, Nicola Curry, Sri V V Deevi, Kate Downes, Daniel Duarte, Kim Elliott, Emanuela Falcinelli, Bruce Furie, David KeelingMichele P Lambert, Rachel Linger, Sarah Mangles, Rutendo Mapeta, Carolyn M Millar, Christopher J Penkett, David J Perry, Kathleen Stirrups, Ernest Turro, Sarah K Westbury, John Wu, NIHR BioResource, Keith Gomez, Kathleen Freson, Willem H Ouwehand, Paolo Gresele, Ilenia Simeoni

Research output: Contribution to journalArticle (Academic Journal)peer-review

28 Citations (Scopus)
191 Downloads (Pure)


The heterogeneous manifestations of MYH9‐related disorder (MYH9‐RD), characterized by macrothrombocytopenia, Döhle‐like inclusion bodies in leukocytes, bleeding of variable severity with, in some cases, ear, eye, kidney, and liver involvement, make the diagnosis for these patients still challenging in clinical practice. We collected phenotypic data and analyzed the genetic variants in more than 3,000 patients with a bleeding or platelet disorder. Patients were enrolled in the BRIDGE‐BPD and ThromboGenomics Projects and their samples processed by high throughput sequencing (HTS). We identified 50 patients with a rare variant in MYH9. All patients had macrothrombocytes and all except two had thrombocytopenia. Some degree of bleeding diathesis was reported in 41 of the 50 patients. Eleven patients presented hearing impairment, three renal failure and two elevated liver enzymes. Among the 28 rare variants identified in MYH9, 12 were novel. HTS was instrumental in diagnosing 23 patients (46%). Our results confirm the clinical heterogeneity of MYH9‐RD and show that, in the presence of an unclassified platelet disorder with macrothrombocytes, MYH9‐RD should always be considered. A HTS‐based strategy is a reliable method to reach a conclusive diagnosis of MYH9‐RD in clinical practice.
Original languageEnglish
Number of pages14
JournalHuman Mutation
Early online date28 Sept 2019
Publication statusE-pub ahead of print - 28 Sept 2019


  • ACMG guidelines
  • clinical diagnosis
  • genomics
  • high throughput sequencing
  • MYH9‐related disorders
  • variant classification


Dive into the research topics of 'Next-generation sequencing for the diagnosis of MYH9-RD: predicting pathogenic variants'. Together they form a unique fingerprint.

Cite this