engleski

LGMD2I in Spanish and Croatian Populations

Limb Girdle Muscular Dystrophy type 2I (LGMD2I) is an autosomal recessive muscular dystrophy caused by mutations in the Fukutin Related Protein (FKRP). This gene is located at 19q13.3 and contains four exons. Immunohistochemical analysis is not possible to date because no specific antibodies have been isolated. Thus, mutational analysis is the method to obtain an accurate molecular diagnosis of the disease. The aim of this work is: (1) to diagnose the patients with clinical features suggesting LGMD2I, (2) to observe the frequency of this pathology in these two populations and, (3) to offer genetic counselling to the affected families. We studied 80 Spanish and Croatian patients presenting a LGMD2I phenotype and in whom we previously excluded a dystrophinopathy, a LGMD2A, a LGMD2C and a LGMD2D. The molecular study was performed following two different techniques. First of all, we analyzed the presence of the L276I mutation (reccurrent in North European population) by restriction enzyme analysis. Moreover, we sequenced the exon 4 (unique coding exon of FKRP gene). We found four missense mutations in eleven patients: E55Q, R143S, L276I and G373S. Two of these mutations (E55Q and G373S) has not been previously described. Their pathogenia was demonstrated by the analysis of 50 chromosomes from normal controls and 50 chromosomes from other myopathy patients (sarcoglycanopathies, DMD, BMD, myotonic dystrophy, caveolinopathy). The L276I mutation was identified in eight patients (3 Spanish and 5 Croatian) and should be considered the more frequent FKRP mutation in the populations studied. The low number of FKRP mutations identified despite the patients were very well classified could indicate the low frequency of LGMD2I in these two populations.

LGMD 2I; FKRP

nije evidentirano