Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy

Caroline Godfrey, Diana Escolar, Martin Brockington, Emma M. Clement, Rachael Mein, Cecilia Jimenez-Mallebrera, Silvia Torelli, Lucy Feng, Susan C. Brown, Caroline A. Sewry, Mary Rutherford, Yehuda Shapira, Stephen Abbs, Francesco Muntoni

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Defects in glycosylation of α-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 α-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. Interpretation: 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.

Original languageEnglish (US)
Pages (from-to)603-610
Number of pages8
JournalAnnals of neurology
Volume60
Issue number5
DOIs
StatePublished - Nov 2006

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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