Identification of a biochemical difference between male and female human fibroblasts: implications for the expression of Duchenne muscular dystrophy.

The lysosomal enzyme dipeptidyl aminopeptidase-I (DAP-I) was reduced in Duchenne muscular dystrophy (DMD) fibroblasts to 30% of the level found in age- and sex-matched controls (p less than 0.005). Structure-linked latency, defined as the increase in DAP-I activity caused by disruption of the lysosomal membrane, was also reduced in Duchenne fibroblasts to 70% of normal levels (p less than 0.001). Duchenne carriers and age- and sex-matched control fibroblasts had similar DAP-I activities and latency. However, the similarity of normal and carrier female DAP-I activities was not due to elevation of the carrier female activities to levels similar to normal males, but rather to reduction of all female DAP-I activities to 30% of normal male levels (p less than 0.001). This gave them comparable activities to those of the male DMD cells. One explanation for these unexpected results would require a modification of the genetics of DMD to that of a Y-influenced X-linked model.