Sporadic occurrence of Duchenne muscular dystrophy: evidence for new mutation

Abstract

The mechanism of inheritance of sporadically occurring Duchenne muscular dystrophy has been investigated in 42 families, using carrier detection methods and genetic evaluation. Our studied find that serum CPK detects 72% of female carriers of DMD. Quantitative LDH and/or its isozymes were not found to be a useful means of carrier detection, as reported by Roses et al. (1977). Employing family pedigree data and CPK carrier testing, we determined by Bayesian methods the probability that the mother and maternal grandmother in these families were DMD carriers. These studies revealed 23 families (Category I) with no evidence for DMD carriers, 11 families (Category II) in which the mother was found to be a carrier, and 3 families (Category III) in which both mother and maternal grandmother were found to be carriers. Nineteen of the 42 families have a greater than 83% probability that the sporadic DMD case arose by mutation in a maternal gamete. This finding is in good agreement with the theoretically expected 1/3 of DMD cases arising by new mutation.