Download Genetic and clinical study of LGMD type 2A in seven patients from a

Limb-girdle muscular dystrophy with calpain deficiency(LGMD 2A) in Croatia: a
survey in a small rural community
Canki-Klain Nina(1); Zurak Nikša (1); Leturcq Francoise (2); Recan Dominique (2);
Kaplan Jean -Claude (2); Urtizberea Jan Andoni (3) ; Potocki Kristina (4); Milicic
Davor (5)
(1) Department of Neurology, Zagreb University Medical School, Croatia
(2)Laboratoire de biochimie et Genetique Moleculaire, Paris, France
(3)Institut de Myologie, Hopital de la Salpetriere, Paris, France
(4)Department of Radiology, Zagreb University Medical School, Croatia
(5)University Clinic for Cardiovascular Diseases, Zagreb, Croatia
Autosomal recessive limb-girdle muscular dystrophies (LGMD2) form a group of
muscle diseases presenting great clinical and genetic heterogeneity. They are
characterized by progressive muscular atrophy and weakness of the pelvic and
shoulder girdle and proximal limb muscles, showing considerable variation in age of
onset, evolution, and severity. At least six distinct genetic entities leading to an
LGMD2 have been identified in the last years. They include four genes encoding for
the sarcoglycans, the gene encoding for the calpain 3 (LGMD2A) and the LGMD2B
locus mapped on chromosome 2p. We report seven males (two already deceased) and
two females affected by a muscular dystrophy, similar to the description of juvenile
limb-girdle muscular dystrophy of Reunion Island (Fardeau et al. Brain,1996;119:
295). A detailed clinical and genealogical study of these 9 patients from five
apperently non related families permitted to identify links between the different
nuclear families. Preliminary results of molecular analysis obtained by DGGE in two
families have revealed three homozygous patients (oncle and his niece in one family ;
one of two brothers in the second ) for the mutation 551A. Because of increased
inbreeding, we suspect that the same mutation is the cause of LGMD in other families
as the consequence of founder effect in this village.
Keywords: calpain; clinical characteristics; genetics