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Limb Girdle Muscular Dystrophy Due to Mutations in Pomt2 Publisher Pubmed



Ostergaard ST1 ; Johnson K2 ; Stojkovic T3 ; Krag T1 ; De Ridder W4, 5, 6 ; De Jonghe P4, 5, 6 ; Baets J4, 5, 6 ; Claeys KG7, 8 ; Fernandeztorron R9 ; Phillips L2 ; Topf A2 ; Colomer J10 ; Nafissi S11 ; Jamalomidi S11 Show All Authors
Authors
  1. Ostergaard ST1
  2. Johnson K2
  3. Stojkovic T3
  4. Krag T1
  5. De Ridder W4, 5, 6
  6. De Jonghe P4, 5, 6
  7. Baets J4, 5, 6
  8. Claeys KG7, 8
  9. Fernandeztorron R9
  10. Phillips L2
  11. Topf A2
  12. Colomer J10
  13. Nafissi S11
  14. Jamalomidi S11
  15. Bouchetseraphin C12
  16. Leturcq F13
  17. Macarthur DG14, 15
  18. Lek M14, 15
  19. Xu L14, 15
  20. Nelson I16
  21. Straub V2
  22. Vissing J1
Show Affiliations
Authors Affiliations
  1. 1. Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, Kobenhavn, Denmark
  2. 2. John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom
  3. 3. AP-HP, Institute of Myology, Centre de reference des maladies neuromusculaires Paris Est, G-H Pitie-Salpetriere, France
  4. 4. Neurogenetics Group, Center for Molecular Neurology, Vlaams Instituut voor Biotechnologie, Antwerp, Belgium
  5. 5. Laboratory of Neuromuscular Pathology, Institute Born-Bunge, University of Antwerp, Antwerpen, Belgium
  6. 6. Department of Neurology, Neuromuscular Reference Centre, Antwerp University Hospital, Antwerpen, Belgium
  7. 7. Department of Neurology, Neuromuscular Reference Centre, University Hospitals Leuven, Leuven, Belgium
  8. 8. Department of Neurosciences, Experimental Neurology, Laboratory for Muscle Diseases and Neuropathies, Katholieke Universiteit Leuven, Leuven, Belgium
  9. 9. Department of Neurology, Donostia University Hospital, Biodonostia Health Research Institute, Donostia-San Sebastian, Spain
  10. 10. Servei de Neurologia, Hospital Sant Joan de Deu, Barcelona, Spain
  11. 11. Department of Neurology, Iranian Center of Neurological Research, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  12. 12. Departement de Biochimie et de Genetique, AP-HP, Hopital Bichat, Paris, France
  13. 13. Laboratoire de Genetique et Biologie Moleculaires Hopital Cochin, Paris, France
  14. 14. Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, United States
  15. 15. Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, United States
  16. 16. Center of Research in Myology, Paris, France

Source: Journal of neurology# neurosurgery# and psychiatry Published:2018


Abstract

BACKGROUND: Mutations in the gene coding for protein O-mannosyl-transferase 2 (POMT2) are known to cause severe congenital muscular dystrophy, and recently, mutations in POMT2 have also been linked to a milder limb-girdle muscular dystrophy (LGMD) phenotype, named LGMD type 2N (LGMD2N). Only four cases have been reported so far.ClinicalTrials.gov ID: NCT02759302 METHODS: We report 12 new cases of LGMD2N, aged 18-63 years. Muscle involvement was assessed by MRI, muscle strength testing and muscle biopsy analysis. Other clinical features were also recorded. RESULTS: Presenting symptoms were difficulties in walking, pain during exercise, delayed motor milestones and learning disabilities at school. All had some degree of cognitive impairment. Brain MRIs were abnormal in 3 of 10 patients, showing ventricular enlargement in one, periventricular hyperintensities in another and frontal atrophy of the left hemisphere in a third patient. Most affected muscle groups were hip and knee flexors and extensors on strength testing. On MRI, most affected muscles were hamstrings followed by paraspinal and gluteal muscles. The 12 patients in our cohort carried 11 alleles with known mutations, whereas 11 novel mutations accounted for the remaining 13 alleles. CONCLUSION: We describe the first cohort of patients with LGMD2N and show that unlike other LGMD types, all patients had cognitive impairment. Primary muscle involvement was found in hamstring, paraspinal and gluteal muscles on MRI, which correlated well with reduced muscle strength in hip and knee flexors and extensors. The study expands the mutational spectrum for LGMD2N, with the description of 11 novel POMT2 mutations in the association with LGMD2N. CLINICAL TRIAL REGISTRATION: NCT02759302. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.