Congenital myasthenic syndrome with tubular aggregates caused by GFPT1 mutations

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• 作者：Velina Guergueltcheva (12)
  Juliane S. Müller (3)
  Marina Dusl (1)
  Jan Senderek (45)
  Anders Oldfors (6)
  Christopher Lindbergh (7)
  Susan Maxwell (8)
  Jaume Colomer (9)
  Cecilia Jimenez Mallebrera (9)
  Andres Nascimento (9)
  Juan J. Vilchez (10)
  Nuria Muelas (10)
  Janbernd Kirschner (11)
  Shahriar Nafissi (12)
  Ariana Kariminejad (13)
  Yalda Nilipour (14)
  Bita Bozorgmehr (13)
  Hossein Najmabadi (13)
  Carmelo Rodolico (15)
  J?rn P. Sieb (16)
  Beate Schlotter (1)
  Benedikt Schoser (1)
  Ralf Herrmann (17)
  Thomas Voit (18)
  Ortrud K. Steinlein (19)
  Abdolhamid Najafi (20)
  Andoni Urtizberea (21)
  Doriette M. Soler (22)
  Francesco Muntoni (23)
  Michael G. Hanna (24)
  Amina Chaouch (3)
  Volker Straub (3)
  Kate Bushby (3)
  Jacqueline Palace (25)
  David Beeson (8)
  Angela Abicht (1)
  Hanns Lochmüller (3) hanns.lochmuller@ncl.ac.uk
• 关键词：Congenital myasthenic syndromes – Limb ; girdle myasthenia – Tubular aggregates – GFPT1 – Dok ; 7
• 刊名：Journal of Neurology
• 出版年：2012
• 出版时间：May 2012
• 年：2012
• 卷：259
• 期：5
• 页码：838-850
• 全文大小：844.0 KB
• 参考文献：1. Engel AG, Sine SM (2005) Current understanding of congenital myasthenic syndromes. Curr Opin Pharmacol 5:308–321
  2. Müller JS, Mihaylova V, Abicht A, Lochmuller H (2007) Congenital myasthenic syndromes: spotlight on genetic defects of neuromuscular transmission. Expert Rev Mol Med 9:1–20
  3. McQuillen MP (1966) Familial limb-girdle myasthenia. Brain 89:121–132
  4. Beeson D, Higuchi O, Palace J, Cossins J, Spearman H, Maxwell S, Newsom-Davis J, Burke G, Fawcett P, Motomura M et al (2006) Dok-7 mutations underlie a neuromuscular junction synaptopathy. Science (New York, NY) 313:1975–1978
  5. Ben Ammar A, Petit F, Alexandri N, Gaudon K, Bauche S, Rouche A, Gras D, Fournier E, Koenig J, Stojkovic T et al (2010) Phenotype genotype analysis in 15 patients presenting a congenital myasthenic syndrome due to mutations in DOK7. J Neurol 257:754–766
  6. Müller JS, Herczegfalvi A, Vilchez JJ, Colomer J, Bachinski LL, Mihaylova V, Santos M, Schara U, Deschauer M, Shevell M et al (2007) Phenotypical spectrum of DOK7 mutations in congenital myasthenic syndromes. Brain 130:1497–1506
  7. Palace J, Lashley D, Newsom-Davis J, Cossins J, Maxwell S, Kennett R, Jayawant S, Yamanashi Y, Beeson D (2007) Clinical features of the DOK7 neuromuscular junction synaptopathy. Brain 130:1507–1515
  8. Selcen D, Milone M, Shen XM, Harper CM, Stans AA, Wieben ED, Engel AG (2008) Dok-7 myasthenia: phenotypic and molecular genetic studies in 16 patients. Ann Neurol 64:71–87
  9. Anderson JA, Ng JJ, Bowe C, McDonald C, Richman DP, Wollmann RL, Maselli RA (2008) Variable phenotypes associated with mutations in DOK7. Muscle Nerve 37:448–456
  10. Senderek J, Müller JS, Dusl M, Strom TM, Guergueltcheva V, Diepolder I, Laval SH, Maxwell S, Cossins J, Krause S et al (2011) Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect. Am J Hum Genet 88:162–172
  11. Haltiwanger RS, Lowe JB (2004) Role of glycosylation in development. Annu Rev Biochem 73:491–537
  12. Rodolico C, Toscano A, Autunno M, Messina S, Nicolosi C, Aguennouz M, Laura M, Girlanda P, Messina C, Vita G (2002) Limb-girdle myasthenia: clinical, electrophysiological and morphological features in familial and autoimmune cases. Neuromuscul Disord 12:964–969
  13. Sieb JP, Tolksdorf K, Dengler R, Jerusalem F (1996) An autosomal-recessive congenital myasthenic syndrome with tubular aggregates in a Libyan family. Neuromuscul Disord 6:115–119
  14. Ohno K, Tsujino A, Brengman JM, Harper CM, Bajzer Z, Udd B, Beyring R, Robb S, Kirkham FJ, Engel AG (2001) Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. Proc Natl Acad Sci USA 98:2017–2022
  15. Chevessier F, Bauche-Godard S, Leroy JP, Koenig J, Paturneau-Jouas M, Eymard B, Hantai D, Verdiere-Sahuque M (2005) The origin of tubular aggregates in human myopathies. J Pathol 207:313–323
  16. Slater CR, Fawcett PR, Walls TJ, Lyons PR, Bailey SJ, Beeson D, Young C, Gardner-Medwin D (2006) Pre- and post-synaptic abnormalities associated with impaired neuromuscular transmission in a group of patients with ‘limb-girdle myasthenia’. Brain 129:2061–2076
  17. Azulay JP, Pouget J, Figarella-Branger D, Colamarino R, Pellissier JF, Serratrice G (1994) Isolated proximal muscular weakness disclosing myasthenic syndrome. Rev Neurol (Paris) 150:377–381
  18. Dobkin BH, Verity MA (1978) Familial neuromuscular disease with type 1 fiber hypoplasia, tubular aggregates, cardiomyopathy, and myasthenic features. Neurology 28:1135–1140
  19. Furui E, Fukushima K, Sakashita T, Sakato S, Matsubara S, Takamori M (1997) Familial limb-girdle myasthenia with tubular aggregates. Muscle Nerve 20:599–603
  20. Johns TR, Campa JF, Adelman LS (1973) Familial myasthenia with ‘tubular aggregates’ treated with prednisone. Neurology 73:426
  21. Johns TR, Campa JF, Crowley WJ, Miller JQ (1971) Familial myasthenic myopathy. Neurology 71:449
  22. Zephir H, Stojkovic T, Maurage CA, Hurtevent JF, Vermersch P (2001) Tubular aggregate congenital myopathy associated with neuromuscular block. Rev Neurol (Paris) 157:1293–1296
  23. Schara U, Barisic N, Deschauer M, Lindberg C, Straub V, Strigl-Pill N, Wendt M, Abicht A, Muller JS, Lochmuller H (2009) Ephedrine therapy in eight patients with congenital myasthenic syndrome due to DOK7 mutations. Neuromuscul Disord 19:828–832
  24. Lashley D, Palace J, Jayawant S, Robb S, Beeson D (2010) Ephedrine treatment in congenital myasthenic syndrome due to mutations in DOK7. Neurology 74:1517–1523
  25. Mihaylova V, Müller JS, Vilchez JJ, Salih MA, Kabiraj MM, D’Amico A, Bertini E, Wolfle J, Schreiner F, Kurlemann G et al (2008) Clinical and molecular genetic findings in COLQ-mutant congenital myasthenic syndromes. Brain 131:747–759
  26. Müller JS, Mildner G, Muller-Felber W, Schara U, Krampfl K, Petersen B, Petrova S, Stucka R, Mortier W, Bufler J et al (2003) Rapsyn N88 K is a frequent cause of congenital myasthenic syndromes in European patients. Neurology 60:1805–1810
  27. Cossins J, Burke G, Maxwell S, Spearman H, Man S, Kuks J, Vincent A, Palace J, Fuhrer C, Beeson D (2006) Diverse molecular mechanisms involved in AChR deficiency due to rapsyn mutations. Brain 129:2773–2783
  28. Oki T, Yamazaki K, Kuromitsu J, Okada M, Tanaka I (1999) cDNA cloning and mapping of a novel subtype of glutamine:fructose-6-phosphate amidotransferase (GFAT2) in human and mouse. Genomics 57:227–234
  29. Niimi M, Ogawara T, Yamashita T, Yamamoto Y, Ueyama A, Kambe T, Okamoto T, Ban T, Tamanoi H, Ozaki K et al (2001) Identification of GFAT1-L, a novel splice variant of human glutamine: fructose-6-phosphate amidotransferase (GFAT1) that is expressed abundantly in skeletal muscle. J Hum Genet 46:566–571
  30. Pavlovicova M, Novotova M, Zahradnik I (2003) Structure and composition of tubular aggregates of skeletal muscle fibres. Gen Physiol Biophys 22:425–440
  31. Engel WK, Bishop DW, Cunningham GG (1970) Tubular aggregates in type II muscle fibers: ultrastructural and histochemical correlation. J Ultrastruct Res 31:507–525
  32. Schubert W, Sotgia F, Cohen AW, Capozza F, Bonuccelli G, Bruno C, Minetti C, Bonilla E, Dimauro S, Lisanti MP (2007) Caveolin-1(?/?)- and caveolin-2(?/?)-deficient mice both display numerous skeletal muscle abnormalities, with tubular aggregate formation. Am J Pathol 170:316–333
• 作者单位：1. Department of Neurology, Friedrich-Baur-Institut, Ludwig Maximilians University, Munich, Germany2. Clinic of Neurology, University Hospital Alexandrovska, Sofia, Bulgaria3. Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, NE1 3BZ UK4. Institute of Neuropathology, RWTH Aachen University, Aachen, Germany5. Institute of Human Genetics, RWTH Aachen University, Aachen, Germany6. Department of Pathology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden7. Neuromuscular Center, Sahlgrenska University Hospital, Gothenburg, Sweden8. Neurosciences Group, Department of Clinical Neurology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK9. Unitat de Patologia Neuromuscular, Servei de Neurologia, Hospital Sant Joan de Deu, Esplugues, Barcelona, Spain10. Servicio de Neurología, Hospital Universitario y Politécnico La Fe and CIBER de Enfermedades Neurodegenerativas (CIBERNED), Valencia, Spain11. Division of Neuropaediatrics and Muscle Disorders, University Medical Center, Freiburg, Germany12. Department of Neurology, Tehran University of Medical Sciences, Tehran, Iran13. Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran14. Neuropathology Lab, Toos Hospital, Tehran, Iran15. Departments of Neurosciences, Psychiatry and Anaesthesiology, A.O.U. “G. Martino- Messina, Italy16. Department of Neurology, Geriatric Medicine and Palliative Care, Hanse-Klinikum, Stralsund, Germany17. Department of Paediatrics I, University Hospital Essen, Essen, Germany18. Institut de Myologie, Unité Mixte de Recherche UPMC-INSERM-CNRS-AIM UM 76, U974, UMR 7215, Groupe Hospitalier Pitié-Salpêtrière, Paris, France19. Institute of Human Genetics, Ludwig Maximilians University, Munich, Germany20. Azad University Medical Branch, Tehran, Iran21. H?pital Marin, Hendaye, France22. Department of Paediatrics, Mater Dei Hospital, Tal-Qroqq, Msida, Malta23. The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK24. MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London, UK25. CMS NCG Group, Department of Clinical Neurology, John Radcliffe Hospital, Oxford, UK
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Neurology
  Neurosciences
  Neuroradiology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1459

文摘

Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous group of inherited disorders of the neuromuscular junction. A difficult to diagnose subgroup of CMS is characterised by proximal muscle weakness and fatigue while ocular and facial involvement is only minimal. DOK7 mutations have been identified as causing the disorder in about half of the cases. More recently, using classical positional cloning, we have identified mutations in a previously unrecognised CMS gene, GFPT1, in a series of DOK7-negative cases. However, detailed description of clinical features of GFPT1 patients has not been reported yet. Here we describe the clinical picture of 24 limb-girdle CMS (LG-CMS) patients and pathological findings of 18 of them, all carrying GFPT1 mutations. Additional patients with CMS, but without tubular aggregates, and patients with non-fatigable weakness with tubular aggregates were also screened. In most patients with GFPT1 mutations, onset of the disease occurs in the first decade of life with characteristic limb-girdle weakness and fatigue. A common feature was beneficial and sustained response to acetylcholinesterase inhibitor treatment. Most of the patients who had a muscle biopsy showed tubular aggregates in myofibers. Analysis of endplate morphology in one of the patients revealed unspecific abnormalities. Our study delineates the phenotype of CMS associated with GFPT1 mutations and expands the understanding of neuromuscular junction disorders. As tubular aggregates in context of a neuromuscular transmission defect appear to be highly indicative, we suggest calling this condition congenital myasthenic syndrome with tubular aggregates (CMS-TA).