To the Editor:
In a population, when equilibrium between mutation and selection is reached, a fraction (x) of individuals affected by an X-linked recessive lethal disorder is due to new mutations [Haldane, 19351. Being p, the mutation rate in female germ cells, and v, the mutation rate in male germ cells, x = p / ( 2 p + v). If mutation rates in male and in female gametes are equal, i.e. p = v, x = 0.33.
The proportion of new mutants (x) among cases of Duchenne Muscular Dystrophy (DMD) is matter of debate since 1976 [Roses et al., 19771. A number of papers were produced, in which an estimate of such proportion was attempted [Davie and Emery, 1978; Danieli and Barbujani, 19841. Although conclusive evidence has not thus far been produced, there are indications that the proportion (x) of sporadic cases in DMD might be lower than expected [Russo et al., 19871. This finding might be explained by assuming that the mutation rate is higher in male gametes, as postulated by Vogel [ 19771 and as supported by observations in Lesch-Nyhan syndrome (LNS) and haemophilia A [Vogel and Rathemberg, 1975; Bernardi et al., 19871. However, the use of DNA probes introduced new complexity, by revealing that a substantial fraction of isolated cases of DMD are due to deletions on a large DNA segment in the region Xp21 Robertson, 19871. Deletions are currently interpreted as a result of unequal crossing-overs in the female germ cells (Fig. ), according to the model generally accepted for deletions in the globin genes [Vogel and Motulsky, 19861; moreover, deletions might be generated by crossing-overs occurring in heterozygotes for an inversion including the DMD region [Goodfellow, 19861. The maternal origin of deletional mutations would imply that mutation rate is higher in females than in males; as a consequence, a proportion of sporadic cases higher than 0.33 should be observed. On the other hand, some estimates of the proportion of sporadic cases in DMD seem to suggest just the opposite [Bucher et al.,