LIMB-GIRDLE MUSCULAR-DYSTROPHY IN GUIPUZCOA (BASQUE COUNTRY, SPAIN)

The concept of limb-girdle muscular dystrophy (LGMD) is changing rapid ly due to the advances in molecular genetics. Recently, seven differen t gene loci have been described, demonstrating that limb-girdle muscul ar dystrophy is a heterogeneous syndrome, which includes different dis eases with a similar phenotype, In isolated populations which have lit tle genetic exchange with neighbouring populations, an accumulation of cases may be found. We carried out an epidemiological study in Guipuz coa, a small mountainous Basque province in northern Spain, and found the highest prevalence rate of LGMD described so far: 69 per million. Genetic studies demonstrated that 38 cases corresponded to the LGMD2A type, due to calpain-3 gene mutations, Only one patient with alpha-sar coglycanopathy was found, and in 12 patients the genetic defect was no t identified. Moreover, the particular calpain-3 mutation predominant in Basque chromosomes (exon 22, 2362AG-->TCATCT), has only been rarely found in the rest of the world. This observation strongly suggests a founder effect in the indigenous population of Guipuzcoa, The clinical characteristics of the patients with calpain-3 gene mutations were qu ite homogeneous and different from the other groups (sarcoglycanopathy and unknown gene defect), allowing for a precise clinical diagnostic. The disease onset was betwen the ages of 8 and 15 years, in most case s in the pelvic girdle, and the patients became wheelchair-bound betwe en 11 and 28 years after onset. No pseudohypertrophy of calves or cont ractures were observed. No clear correlations were found between the n ature and site of the mutation and the resulting phenotype.