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Autosomal recessive limb-girdle muscular dystrophies (AR LGMD) represent a group of muscle diseases with a wide spectrum of clinical signs, varying from very severe to mild. Four different loci that when mutated cause the AR LGMD phenotype have been mapped or cloned or both: in two of them the linked families seem to have a relatively mild phenotype (LGMD2a and LGMD2b), in the third one the reported linked families show a more severe clinical course (LGMD2c), while mutations in the fourth locus may cause severe or mild phenotypes (LGMD2d). The relative proportion of each of these genetic forms among the LGMD families and whether there are other genes that when mutated cause this phenotype is unknown. The closest available informative markers for each of the mapped AR LGMD genes have been tested in 13 Brazilian families with at least three affected patients. The findings from the present report confirm non-allelic heterogeneity for LGMD and suggest that in our population about 33% of the LGMD families are caused by mutations in the 15q gene, 33% in the 2p gene, 17% by mutations in the adhalin gene, and less than 10% may be by mutations at the 13q locus. They also suggest that there is at least one other gene responsible for this phenotype. In addition, the main clinical features of the different forms are discussed.

Duchenne-like muscular dystrophy (DLMD) is an autosomal recessive (AR) muscular dystrophy which presents a clinical course indistinguishable from the Xp21 Duchenne muscular dystrophy or DMD. Recently, Othmane et al., based on a linkage study with 13q12 markers in 3 highly inbred DLMD families from Tunisia, suggested that the gene for this myopathy lies in the pericentromeric region of chromosome 13q. It is unknown if there is genetic heterogeneity causing the DLMD phenotype. Therefore, the aim of the present report is to describe the results of linkage analysis in 4 Brazilian DLMD families with 13q12 markers (D13S115 and D13S120), which were also tested for 50DAG. It was possible to exclude the 13q gene at theta = 0.10 as responsible for the DLMD phenotype in our families using both 13q12 markers, if the lod scores of each family were added up. Interestingly, 3 families were deficient for 50 DAG while one showed a positive pattern for this glycoprotein. Therefore, these results suggest: a) the DLMD phenotype is caused by more than one recessive gene; b) a gene, not located at 13q, causes deficiency of 50 DAG as a primary or secondary defect.

The gene responsible for facioscapulohumeral muscular dystrophy (FSHD), an autosomal dominant neuromuscular condition, has been mapped to chromosome 4. Until recently, the two closest available markers were D4S139 and D4S163 but a new marker (p13E-11) which recognizes de novo rearrangements in isolated cases of FSHD characterized by shorter EcoRI fragments has been now identified. Linkage analysis in FSHD families with p13E-11 shows that usually a smaller fragment segregates with the disease gene among the affected individuals from each genealogy. In the present paper, we report the results from linkage analysis with the marker loci D4S163 and D4S139 in 6 FSHD families and with p13E-11 in these and in 6 other additional Brazilian families (total of 12). The results from such analysis do not suggest genetic heterogeneity for FSHD in our population. In 11 out of the 12 families studied with p13E-11, a shorter specific EcoRI band was found to segregate in all affected patients from each genealogy. In one family, the normal individuals had a smaller EcoRI fragment than the affected ones. The size of the EcoRI fragments detected with p13E-11 varied from 13.5 to 29 kb but was constant within each genealogy. Our results suggest that the use of the marker p13E-11 for preclinical and prenatal diagnosis should be done only in families in which it is possible to identify the fragments segregating among the affected individuals.