Registry for MYH9-related disease in brief for non-Italian people
Welcome to the web site of the Italian Registry for MYH9-related disease.
MYH9-Related Disease (MYH9-RD)
MYH9-RD is a rare autosomal dominant disorder deriving from mutations of MYH9, the gene for the heavy chain of non-muscle myosin IIA.
All patients present with thrombocytopenia and large platelets since birth, and many of them subsequently develop hearing loss,
cataract and/or a nephropathy that often evolves to end-stage renal failure. Until recently, these patients were referred as
affected by May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome or Epstein syndrome depending on their clinical manifestations
at diagnosis. However, since these disorders are all caused by mutations of MYH9 and their clinical pictures overlap and often
worsen over time, MYH9-RD is the term proposed to include all of them.
The Italian Registry MYH9-RD
Why joining the Italian Registry for MYH9-RD
The Italian Registry for MYH9-related disease has been created and approved by the Institutional Review Board of the
IRCCS Policlinico San Matteo Foundation, Pavia, Italy, in the year 2006. At present (2008), it includes more than 100 institutions
that in the last two years enrolled more than 150 patients.
Although the Registry has been established to develop a network of Italian centers-physicians interested in MYH9-RD,
collaborations with clinicians in other countries is encouraged to improve our knowledge on this rare disease, which will
allow us to better manage patients and their families.
The main aims of the Registry are:
- - To raise awareness of this rare disorder
- - To facilitate diagnosis
- - To define epidemiology
- - To identify genotype/phenotype correlations
- - To improve management of patients
- - To support pathogenetic studies
The Registry has already attained some goals. In particular, in a case series of 108 patients from 50 families a genotype/phenotype
correlation was identified for the most common mutations (Hum Mutat 2008;29:409-17). In brief, most carriers of mutations in
the motor domain of myosin-9 have severe thrombocytopenia and a high risk of developing glomerulonephritis and deafness, while
patients with mutations affecting the rod tail domain show a mild phenotype.
Moreover, thanks to the Registry evidences suggesting that the blockade of the renin-angiotensin system can modify the clinical
course of the kidney disease were also reported (Nephrol Dial Transplant 2008;23:2690-2).
Improving knowledge of MYH9-RD:
How to join the Italian Registry for MYH9-RD
Physicians referring their patients to the Registry will contribute to the creation of a large patient database and will be
considered co-authors of the resulting publications. Moreover, they will be free to report their cases in separate papers.
Facilitating diagnosis of MYH9-RD:
The Registry supplies the immunofluorescence test for MYH9-RD free of charge.
This test evaluates distribution of the heavy chain of non-muscle myosin IIA in the cytoplasm
of neutrophils and can be performed on shipped peripheral blood smears. In our experience, it has 100% sensitivity,
while its specificity is a little lower. Thus, a negative test excludes MYH9-RD, while a positive test requires
confirmation by mutational screening. In case the screening test is positive, the Registry offers the genetic
testing of the most frequently affected coding MYH9 exons free of charge.
When a physician suspects MYH9-RD, he can contact dr. Alessandro Pecci (firstname.lastname@example.org
dr. Carlo Balduini (email@example.com
to arrange sample shipping (peripheral blood films for the immunofluorescence test and anticoagulated blood for mutational screening).
After receiving the samples, the result is communicated to the physician in a few days. If the immunofluorescence test is positive,
the physician is asked to fill in a form in order to collect a series of patient's information to be included in the database.
Then, if patient's genomic DNA is available, mutational screening is carried out analyzing the most commonly affected exons.
Whenever mutations are not identified, the physician can contact directly geneticians dr. Anna Savoia (firstname.lastname@example.org
or dr. Marco Seri (email@example.com
) to arrange further investigation.