Autosomal dominant limb-girdle muscular dystrophy A large kindred with evidence for anticipation

Background: Fourteen genetically distinct forms of limb-girdle muscular dystrophy (LGMD) have been identified, including five types of autosomal dominant LGMD (AD-LGMD). Objective: To describe clinical, histologic, and genetic features of a large Spanish kindred with LGMD and apparent autosomal dominant inheritance spanning five generations. Method: The authors examined 61 members of the family; muscle biopsies were performed on five patients. Linkage analysis assessed chromosomal loci associated with other forms of AD-LGMD. Results: A total of 32 individuals had weakness of the pelvic and shoulder girdles. Severity appeared to worsen in successive generations. Muscle biopsy findings were nonspecific and compatible with MD. Linkage analysis to chromosomes 5q31, 1q11-q21, 3p25, 6q23, and 7q demonstrated that this disease is not allelic to LGMD forms 1A, 1B, 1C, 1D, and 1E. Conclusions: This family has a genetically distinct form of AD-LGMD. The authors are currently performing a genome-wide scan to identify the disease locus.