NGS as a diagnostic tool for unexplained limb-girdle muscles weakness: Results of European MYO-SEQ project in 75 Polish patients

• Autorzy: Lusakowska A. , Johnson K. , Topf A. , Bertoli M. , Phillips L. , Straub V. , Lek M. , Xu L. , MacArthur D.G. , Macias A. , Potulska-Chromik A. , Kierdaszuk B. , Janiszewska K. , Arendt E. , Grochowski P. , Kaminska A. , Kostera-Pruszczyk A.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Hereditary muscle disorders are a genetically heterogeneous group of rare diseases with overlapping phenotypes causing difficulties in establishing a diagnosis. Genetic testing isthe only reliable tool to confirm a prompt diagnosis.Genetically confirmed diagnosisisrequired forthe future targeted therapies and the genetic counselling. Department of Neurology, Warsaw Medical University, participated in a European multicenter project MYO‑SEQ led by Institute of Genetic Medicine, Newcastle University. AIM(S): The main aim of the project was to establish accurate diagnoses in patients with unexplained limb-girdle muscle weakness by applying New Generation Sequencing(NGS). MATERIAL Patients included in the study were at least 10 years old, presented with unexplained limb-girdle or respiratory muscle weakness and/or elevated serum CK activity. Based on these criteria we identified 75 patients treated at our Department of Neurology. METHOD(S): With the patients’ consent, their encoded DNA samples and anonymous clinical data were sent to the MYO‑SEQ coordinating center for a whole exome sequencing using NGS. A detailed analysis of potential mutations was restricted to 169 gene associated with neuromuscular disorders. When the molecular result were obtained, a detail clinical-genetic analysis was done. RESULTS: In total of 75 tested samples, 50 (66,7%) showed specific mutations responsible for the patients’ symptoms, including 45 (60,0%) with mutation in a single gene. In 5 samples (6,7%), mutations in more than one gene were found. In two patients the treatable diseases were identified: Pompe disease and congenital myasthenic syndrome. In 25 (33,3%) samples, no strong candidate gene was identified. CONCLUSIONS: NGS offers an accurate and reliable methodology to establish a diagnosis in rare inherited muscle diseases.When the new molecular therapies become available, NGS test should be included in a standard diagnostic procedure of myopathies.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.76

Twórcy

autor

Lusakowska A.

• Department of Neurology, Medical University of Warsaw, Warsaw, Poland

autor

Johnson K.

• John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, UK

autor

Topf A.

• John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, UK

autor

Bertoli M.

• John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, UK

autor

Phillips L.

• John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, UK

autor

Straub V.

• John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, UK

autor

Lek M.

• Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, USA
• Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, USA

autor

Xu L.

• Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, USA
• Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, USA

autor

MacArthur D.G.

• Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, USA
• Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, USA

autor

Macias A.

• Department of Neurology, Medical University of Warsaw, Warsaw, Poland

autor

Potulska-Chromik A.

• Department of Neurology, Medical University of Warsaw, Warsaw, Poland

autor

Kierdaszuk B.

• Department of Neurology, Medical University of Warsaw, Warsaw, Poland

autor

Janiszewska K.

• Department of Neurology, Medical University of Warsaw, Warsaw, Poland

autor

Arendt E.

• Students’ Scientific Group by the Department of Neurology, Medical University of Warsaw, Warsaw, Poland

autor

Grochowski P.

• Students' Scientific Group by the Department of Neurology, Medical University of Warsaw, Warsaw, Poland

autor

Kaminska A.

• Department of Neurology, Medical University of Warsaw, Warsaw, Poland

autor

Kostera-Pruszczyk A.

• Department of Neurology, Medical University of Warsaw, Warsaw, Poland