Limb–girdle muscular dystrophy: Diagnostic evaluation, frequency and clues to pathogenesis

Lo, Harriet P.; Cooper, Sandra T.; Evesson, Frances J.; Seto, Jane T.; Chiotis, Maria; Tay, Valerie; Compton, Alison G.; Cairns, Anita G.; Corbett, Alistair; MacArthur, Daniel G.; Yang, Nan; Reardon, Katrina; North, Kathryn N.

doi:10.1016/j.nmd.2007.08.009

« Previous Next »Neuromuscular Disorders
Volume 18, Issue 1 , Pages 34-44, January 2008

Limb–girdle muscular dystrophy: Diagnostic evaluation, frequency and clues to pathogenesis

Harriet P. Lo
- Institute for Neuromuscular Research, The Children’s Hospital at Westmead, Sydney, Australia
Sandra T. Cooper
- Institute for Neuromuscular Research, The Children’s Hospital at Westmead, Sydney, Australia
- Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Sydney, Australia
Frances J. Evesson
- Institute for Neuromuscular Research, The Children’s Hospital at Westmead, Sydney, Australia
Jane T. Seto
- Institute for Neuromuscular Research, The Children’s Hospital at Westmead, Sydney, Australia
- Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Sydney, Australia
Maria Chiotis
- Centre for Clinical Neurosciences and Neurological Research, St. Vincent’s Hospital, Melbourne, Australia
Valerie Tay
- Centre for Clinical Neurosciences and Neurological Research, St. Vincent’s Hospital, Melbourne, Australia
Alison G. Compton
- Institute for Neuromuscular Research, The Children’s Hospital at Westmead, Sydney, Australia
Anita G. Cairns
- Institute for Neuromuscular Research, The Children’s Hospital at Westmead, Sydney, Australia
Alistair Corbett
- Concord Repatriation General Hospital, Sydney, Australia
Daniel G. MacArthur
- Institute for Neuromuscular Research, The Children’s Hospital at Westmead, Sydney, Australia
- Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Sydney, Australia
Nan Yang
- Institute for Neuromuscular Research, The Children’s Hospital at Westmead, Sydney, Australia
Katrina Reardon
- Centre for Clinical Neurosciences and Neurological Research, St. Vincent’s Hospital, Melbourne, Australia
Kathryn N. North
- Institute for Neuromuscular Research, The Children’s Hospital at Westmead, Sydney, Australia
- Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Sydney, Australia
- Corresponding author. Address: Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Sydney, Australia. Tel.: +61 2 98451906; fax: +61 2 98453389.

Received 23 July 2007; received in revised form 23 July 2007; accepted 17 August 2007.

Abstract

We characterized the frequency of limb–girdle muscular dystrophy (LGMD) subtypes in a cohort of 76 Australian muscular dystrophy patients using protein and DNA sequence analysis. Calpainopathies (8%) and dysferlinopathies (5%) are the most common causes of LGMD in Australia. In contrast to European populations, cases of LGMD2I (due to mutations in FKRP) are rare in Australasia (3%). We have identified a cohort of patients in whom all common disease candidates have been excluded, providing a valuable resource for identification of new disease genes. Cytoplasmic localization of dysferlin correlates with fiber regeneration in a subset of muscular dystrophy patients. In addition, we have identified a group of patients with unidentified forms of LGMD and with markedly abnormal dysferlin localization that does not correlate with fiber regeneration. This pattern is mimicked in primary caveolinopathy, suggesting a subset of these patients may also possess mutations within proteins required for membrane targeting of dysferlin.

Keywords: Limb–girdle muscular dystrophy, Dysferlin