[Show abstract][Hide abstract] ABSTRACT: Autosomal recessive limb-girdle muscular dystrophies (AR LGMD) represent a heterogeneous group of diseases with a wide spectrum
of clinical variability, classified phenotypically into two main groups, the most severe forms (Duchenne-like muscular dystrophy,
DLMD, or severe childhood autosomal recessive muscular dystrophy, SCARMD) and the milder forms. Four genes causing AR LGMD
have been mapped: the 15q (LGMD2a), the 2p (LGMD2b), the 13q locus (LGMD2c) and the adhalin gene on chromosome 17q (LGMD2d).
In the present report we have performed linkage analysis with 17q markers in three mild AR LGMD and in four DLMD families
with adhalin deficiency and unlinked to 2p, 15q or 13q genes. Linkage was observed only among the mild cases. Patients from
these three 17q-linked families showed near or total deficiency of adhalin in muscle biopsies. An identical missense mutation
was identified in all three 17q-linked unrelated families. These results indicate that AR LGMD with a mild phenotype is caused
by mutations in the adhalin gene. In addition, they demonstrate that there is at least one other locus for DLMD associated
with adhalin deficiency.
Human Molecular Genetics 08/1995; 4(7):1163-7. DOI:10.1093/hmg/4.7.1163 · 6.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In a survey of 454 families with patients affected with Duchenne muscular dystrophy (DMD) we have found 4 genealogies with 2 or more affected patients who were related through paternal lines. In 1 of these families, 2 affected cousins showed different DNA deletions suggesting 2 independent mutations; in the other 2, in which only the propositus could be studied, DNA deletions were also detected in the dystrophin gene. In the last one, with 3 affected patients, no DNA deletions were detected but immunohistochemical study of muscle biopsies showed a negative dystrophin pattern typical of DMD.
Although one of these families might have occurred by chance, the probability of finding the other 3 in our sample of families with DMD patients constitutes a rare event. It is suggested that other mechanisms, such as the presence of transposable elements in other sites of the genome, could be responsible in some families, for a greater predisposition for the occurrence of pathogenic deletions, duplications or mutations.
American Journal of Medical Genetics 01/1991; 38(1):80 - 84. DOI:10.1002/ajmg.1320380118 · 3.23 Impact Factor