HIGH PROPORTION OF NEW MUTATIONS AND POSSIBLE ANTICIPATION IN BRAZILIAN FACIOSCAPULOHUMERAL MUSCULAR-DYSTROPHY FAMILIES

A gene responsible for facioscapulohumeral muscular dystrophy (FSHD) h as been localized at 4q35. Subsequently, it was found that probe p13E- 11 detects a polymorphic EcoRI fragment, usually >28 kb, in normal ind ividuals, whereas in sporadic and familial FSHD cases, an EcoRI fragme nt, usually <28 kb, was found. Although these findings have been amply confirmed, several aspects are as yet either controversial or unsolve d. In the present investigation, 34 Brazilian FSHD families were studi ed at the clinical and the molecular level for the following purposes: to assess the frequency of new mutations and their effect on estimate s of biological fitness, to characterize FSHD-associated EcoRI fragmen ts detected with probe p13E-11 in familial-as compared with isolated-F SHD cases, and to assess whether anticipation occurs in multigeneratio nal families. Results from our study suggest that new mutations are ap parently frequent for FSHD and may account for at least one-third of t he cases, that somatic mosaicism may not be rare, and that biological fitness appeared to be reduced in FSHD, ranging from 0.6 to 0.82 by di fferent estimates, with no difference in sexes. Interestingly, the siz e of the new EcoRI fragment is apparently smaller in more severely aff ected isolated patients. Moreover, the age at onset of clinical signs, as well as the age at ascertainment, in patients from multigeneration al families suggests that anticipation occurs for FSHD in the majority of the families.