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Expanding the Importance of Hmerf Titinopathy: New Mutations and Clinical Aspects Publisher Pubmed



Palmio J1 ; Leonardlouis S2 ; Sacconi S3 ; Savarese M4 ; Penttila S1 ; Semmler AL5, 6 ; Kress W7 ; Mozaffar T8 ; Lai T8 ; Stojkovic T9 ; Berardo A10 ; Reisin R10 ; Attarian S11 ; Urtizberea A12 Show All Authors
Authors
  1. Palmio J1
  2. Leonardlouis S2
  3. Sacconi S3
  4. Savarese M4
  5. Penttila S1
  6. Semmler AL5, 6
  7. Kress W7
  8. Mozaffar T8
  9. Lai T8
  10. Stojkovic T9
  11. Berardo A10
  12. Reisin R10
  13. Attarian S11
  14. Urtizberea A12
  15. Cobo AM12
  16. Maggi L13
  17. Kurbatov S14, 15
  18. Nikitin S15
  19. Milisenda JC16
  20. Fatehi F17
  21. Raimondi M18
  22. Silveira F19
  23. Hackman P4
  24. Claeys KG20, 21
  25. Udd B1, 4, 22
Show Affiliations
Authors Affiliations
  1. 1. Department of Neurology, Neuromuscular Research Center, Tampere University Hospital and University of Tampere, Tampere, 33014, Finland
  2. 2. Institute of Myology, National Reference Center for Neuromuscular Disorders, University Hospital of Salpetriere, UPMC, Paris, France
  3. 3. Nice University Hospital, Universite Cote d’Azur, Nice, France
  4. 4. Folkhalsan Institute of Genetics and Medicum, Haartman Institute, University of Helsinki, Helsinki, Finland
  5. 5. Department of Neurology, RWTH Aachen University, Aachen, Germany
  6. 6. Institute of Neuropathology, RWTH Aachen University, Aachen, Germany
  7. 7. Institute of Human Genetics, University of Wurzburg, Wurzburg, Germany
  8. 8. Neurology Department, University of California, Irvine, Orange, CA, United States
  9. 9. Center of Research in Myology, UPMC Univ Paris, INSERM UMRS, Institut de Myologie, Sorbonne Universites, Paris, France
  10. 10. Neuromuscular Unit, British Hospital, Buenos Aires, Argentina
  11. 11. Reference Center for Neuromuscular Disorders and ALS, CHU La Timone 1338, Marseille, France
  12. 12. Centre de Competences Maladies Neuromusculaires Hendaye, Hendaye, France
  13. 13. Neuroimmunology and Neuromuscular Diseases Unit, Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy
  14. 14. Regional Medical Diagnostic Centre, Voronezh, Russian Federation
  15. 15. Regional Non-governmental Organization «Society of Neuro-Muscular Diseases Specialists», Moscow, Russian Federation
  16. 16. Muscle Research Unit, Internal Medicine Service, Hospital Clinic de Barcelona and CIBERER, Barcelona, Spain
  17. 17. Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
  18. 18. Clinica Moncucco, Via Moncucco 10, Lugano, 6900, Switzerland
  19. 19. Hospital Sao Joao Porto, Porto, Portugal
  20. 20. Department of Neurology, University Hospitals Leuven, Leuven, Belgium
  21. 21. Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, Leuven, Belgium
  22. 22. Department of Neurology, Vaasa Central Hospital, Vaasa, Finland

Source: Journal of Neurology Published:2019


Abstract

Objective: Hereditary myopathy with early respiratory failure (HMERF) is caused by titin A-band mutations in exon 344 and considered quite rare. Respiratory insufficiency is an early symptom. A collection of families and patients with muscle disease suggestive of HMERF was clinically and genetically studied. Methods: Altogether 12 new families with 19 affected patients and diverse nationalities were studied. Most of the patients were investigated using targeted next-generation sequencing; Sanger sequencing was applied in some of the patients and available family members. Histological data and muscle MRI findings were evaluated. Results: Three families had several family members studied while the rest were single patients. Most patients had distal and proximal muscle weakness together with respiratory insufficiency. Five heterozygous TTN A-band mutations were identified of which two were novel. Also with the novel mutations the muscle pathology and imaging findings were compatible with the previous reports of HMERF. Conclusions: Our collection of 12 new families expands mutational spectrum with two new mutations identified. HMERF is not that rare and can be found worldwide, but maybe underdiagnosed. Diagnostic process seems to be complex as this study shows with mostly single patients without clear dominant family history. © 2019, The Author(s).