The facioscapulohumeral muscular dystrophy (FSHD1) gene affects males more severely and more frequently than females.
We investigated 52 families of patients with facioscapulohumeral muscular dystrophy (FSHD1), including 172 patients (104 males and 68 females). Among 273 DNA samples which were analyzed with probe p13E-11, 131 (67 males and 64 females) were shown to carry an EcoRI fragment smaller than 35 kb; 114 among them were examined clinically and neurologically. Results of the present investigation showed that: a) there is no molecular evidence for autosomal or X-linked recessive inheritance of FSHD1; b) an excess of affected males, which is explained by a significantly greater proportion of females than males among asymptomatic cases and a significantly greater proportion of affected sons than daughters observed in the offspring of asymptomatic mothers; c) the penetrance of the FSHD1 gene until age 30 was estimated as 83% for both sexes but was significantly greater for males (95%) than for females (69%); d) new mutations occur significantly more frequently in females than males among somatic/germinal mosaic cases; and e) severely affected cases originated more often through new mutations or were transmitted through maternal than through paternal lines including somatic/germinal mothers. These observations have important implications for understanding the molecular mechanisms responsible for FSHD1 and for genetic and prognostic counseling according to the gender of the affected patient.
Zatz
M
M
Departamento de Biologia, Instituto de Biociências, Universidade de São Paulo, Brazil.
Marie
S K
SK
Cerqueira
A
A
Vainzof
M
M
Pavanello
R C
RC
Passos-Bueno
M R
MR
D000293:Adolescent; D000328:Adult; D002648:Child; D015246:Deoxyribonuclease EcoRI; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D009030:Mosaicism / Q000235:genetics; D009136:Muscular Dystrophies / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D011506:Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins; D017384:Sequence Deletion; D012737:Sex Factors
C101270:FRG1 protein, human; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D015246:Deoxyribonuclease EcoRI