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

Background: Fourteen genetically distinct forms of limb-girdle muscular dys trophy (LGMD) have been identified, including five types of autosomal domin ant LC;MD (AD-LGMD). Objective: To describe clinical, histologic, and genet ic features of a large Spanish kindred with LGMD and apparent autosomal dom inant inheritance spanning five generations. Method: The authors examined 6 1 members of the family; muscle biopsies were performed on five patients. L inkage analysis assessed chromosomal loci associated with other forms of AD -LGMD. Results: A total of 32 individuals had weakness of the pelvic and sh oulder girdles. Severity appeared to worsen in successive generations. Musc le biopsy findings were nonspecific and compatible with MD. Linkage analysi s to chromosomes 5q31, 1q11l-q21, 3p25, 6q23, and 7q demonstrated that this disease is not allelic to LGMD forms LA, 1B, 1C, 1D, and 1E. Conclusions: This family has a genetically distinct form of AD-LGMD. The authors are cur rently performing a genome-wide scan to identify the disease locus.