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Onderzoek in Parijs: klinische kenmerken en spierafwijkingen in NEM6 myopathie
Nicol Voermans

20-06-2017 21:13

Elucidating the role of KBTBD13 in muscle function:
The histopathology of nemaline myopathy type 6 (NEM6)

Supervisor (Radboudumc)
B. Kusters (pathology) and N.C. Voermans (neurology)

Supervisor (abroad)
N. Romero (pathology) and E. Malfatti (myology - neurology)
University Hôpital de la Salpêtrière, Institute of Myology
Department/research institute Pathology and Myology (neurology)

Description of the project
Background. In 2002, our group described a large Dutch family with a novel type of nemaline myopathy (NEM6) with severe muscle slowness. In 2010, the implicated gene was discovered: KBTBD13. The recognition of patients with NEM6, as well as their care and treatment, is severely hampered by the paucity of data regarding the disease phenotype and histopathology. Worldwide, only 50 patients have been identified, partly due to underdiagnosis.

Research questions
1) What are the clincial features of NEM6?
2) What are the histopathological and electromicroscopic hallmarks of NEM6?
This is expected to increase insight in the role of the KBTBD13 gene in the pathophysiology of this myopathy.

Workplan/tasks for the student
During preparation in Nijmegen (start in September – December 2017)
1) Identify all patients in Europe by contacting the neurologists involved (Italy; Spain; Netherlands –they have already expressed their willingness to collaborate), and in other countries (Australia), collect the main clinical data (muscle weakness pattern, other muscle features, mutation in KBTBD13), and create a database;
2) Participate in a prospective study of the clinical phenotype of this cohort with PhD student;
3) Get introduced in single fibre measurements at the VUMC by prof.C. Ottenheijm;
4) Collect available biopsies of NEM6 patients

Scientific period in Paris (first semester of 2018):
5) Describe the typical features of histopathology, immunohistochemistry and electronmicroscopy of the NEM6 biopsies with prof. N Romero and dr. E. Malfatti, experts on the histopathology of nemaline myopathies (in Paris). Especially the obvious more “myofibrillar” pathology in this otherwise nemaline myopathiy will be investigated. This will be under close supervision of both supervisors, prof. Romero and dr.Malfatti, who have already evaluated part of the biopsies.

Factors that jeopardize the feasibility of the workplan: We have an intensive and longstanding collaboration with the Institute of myology of the famous Hôpital de la Salpêtrière. Over the past years, five medical students have worked as a medical student at the institute and had a very pleasant and inspiring time. They have been able to publish their results or are in the process of doing so. They are avaiable for practical advices (housing, language course, additional funding applications). This is a collaboration between the department of neurology and pathology at the Radboudumc, and the institute of Myology.

4 - 6 months (1-3 months preparation; 3 months in Paris)
If the duration is extended to 6 months the student can apply for the Disciplinary Honours Programme for Master's students: