title: Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy.
abstract: OBJECTIVE
  Defects in glycosylation of alpha-dystroglycan are associated with several forms of muscular dystrophy, often characterized by congenital onset and severe structural brain involvement, collectively known as dystroglycanopathies. Six causative genes have been identified in these disorders including fukutin. Mutations in fukutin cause Fukuyama congenital muscular dystrophy. This is the second most common form of muscular dystrophy in Japan and is invariably associated with mental retardation and structural brain defects. The aim of this study was to determine the genetic defect in two white families with a dystroglycanopathy.
  
  
  METHODS
  The six genes responsible for dystroglycanopathies were studied in three children with a severe reduction of alpha-dystroglycan in skeletal muscle.
  
  
  RESULTS
  We identified pathogenic fukutin mutations in these two families. Affected children had normal intelligence and brain structure and shared a limb girdle muscular dystrophy (LGMD) phenotype, had marked elevation of serum creatine kinase, and were all ambulant with remarkable steroid responsiveness.
  
  
  CONCLUSIONS
  Our data suggest that fukutin mutations occur outside Japan and can be associated with much milder phenotypes than Fukuyama congenital muscular dystrophy. These findings significantly expand the spectrum of phenotypes associated with fukutin mutations to include this novel form of limb girdle muscular dystrophy that we propose to name LGMD2L.
authors.affiliation: DNA Laboratory, Genetics Centre, Guy's Hospital, London, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Godfrey
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, George Washington University, Washington, DC.
authors.forename: Diana
authors.initials: D
authors.lastname: Escolar
authors.affiliation: Dubowitz Neuromuscular Centre, Department of Paediatrics, Hammersmith Campus, Imperial College London, London.
authors.forename: Martin
authors.initials: M
authors.lastname: Brockington
authors.affiliation: Dubowitz Neuromuscular Centre, Department of Paediatrics, Hammersmith Campus, Imperial College London, London.
authors.forename: Emma M
authors.initials: EM
authors.lastname: Clement
authors.affiliation: DNA Laboratory, Genetics Centre, Guy's Hospital, London, United Kingdom.
authors.forename: Rachael
authors.initials: R
authors.lastname: Mein
authors.affiliation: Dubowitz Neuromuscular Centre, Department of Paediatrics, Hammersmith Campus, Imperial College London, London.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Jimenez-Mallebrera
authors.affiliation: Dubowitz Neuromuscular Centre, Department of Paediatrics, Hammersmith Campus, Imperial College London, London.
authors.forename: Silvia
authors.initials: S
authors.lastname: Torelli
authors.affiliation: Dubowitz Neuromuscular Centre, Department of Paediatrics, Hammersmith Campus, Imperial College London, London.
authors.forename: Lucy
authors.initials: L
authors.lastname: Feng
authors.affiliation: Dubowitz Neuromuscular Centre, Department of Paediatrics, Hammersmith Campus, Imperial College London, London.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Brown
authors.affiliation: Dubowitz Neuromuscular Centre, Department of Paediatrics, Hammersmith Campus, Imperial College London, London.|Centre for Inherited Neuromuscular Disorders, Robert Jones & Agnes Hunt Orthopaedic Hospital, Oswestry, London, United Kingdom.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sewry
authors.affiliation: Robert Steiner Magnetic Resonance Unit, Clinical Sciences Centre, Hammersmith Hospital, Imperial College London, London, United Kingdom.
authors.forename: Mary
authors.initials: M
authors.lastname: Rutherford
authors.affiliation: Division of Child Neurology, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Shapira
authors.affiliation: DNA Laboratory, Genetics Centre, Guy's Hospital, London, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Abbs
authors.affiliation: Dubowitz Neuromuscular Centre, Department of Paediatrics, Hammersmith Campus, Imperial College London, London.
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D049030:Dystroglycans / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism; D049288:Muscular Dystrophies, Limb-Girdle / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation / Q000235:genetics*; D011241:Prednisone / Q000627:therapeutic use; D035781:Siblings
chemical_list: D000893:Anti-Inflammatory Agents; C113587:FKTN protein, human; D008565:Membrane Proteins; D049030:Dystroglycans; D011241:Prednisone