Xth International Congress on Neuromuscular Disorders, Vancouver, Canada, 2002.
FKRP GENE MUTATED IN LIMB GIRDLE MUSCULAR DYSTROPHY 2I
Adel Driss*, Saturo Noguchi*, Rim Amouri**, Faycal Hentati**, Ichizo Nishino*
* National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo, Japan.
** National Institute of Neurology, La Rabta, Tunis, Tunisia.
Objective: Limb girdle muscular dystrophies (LGMD) are a clinically and genetically heterogeneous group of disorders characterized by skeletal muscle weakness and dystrophic changes in the muscle. They are classified by the localization of the defective genes. We previously reported the localization of a new autosomal recessive form of LGMD mapped on chromosome 19q13.3 and named LGMD 2I.
Methods: This study was carried out on a large consanguineous Tunisian family including 16 affected patients. All patients in this family showed similar phenotypes with progressive limb girdle muscular weakness, a high serum CK and dystrophic changes in muscle biopsy.
Results: Immunohistochemical analysis showed a normal presence of dystrophin, sarcoglycan subunits, sarcospan and beta-dystroglycan, but a marked reduction in alfa-dystroglycan and laninin-alfa2. A positional cloning approach revealed two homozygote mutations on the Fukutin-related protein (FKRP) gene for this family.
Conclusions: Recently, mutations in this gene have been reported either in some families affected with LGMD and in a severe form of congenital muscular dystrophy (MDC1C). Our study finds that this gene can be the causative gene for LGMD 2I.