Evidence for anticipation and association of deletion size with severity in facioscapulohumeral muscular dystrophy. The FSH-DY Group.
Facioscapulohumeral muscular dystrophy (FSHD) is characterized by marked inter- and intrafamilial heterogeneity in its clinical expression. The contribution of genetic factors to this variability is not well characterized. We examined the relationship of phenotype to genotype in a clinically and genetically well-defined FSHD population. Quantitative isometric myometry (QMT) scores, normalized for age, gender, and height, were used to quantify disease severity. We found a significant (r = 0.92, p < 0.004) correlation between disease severity and the size of the 4q35-associated deletion. In addition, when relative disease severity of parent-offspring pairs was compared, the offspring were found to be significantly more severely affected (p = 0.011). This generational effect suggests the presence of anticipation in FSHD and raises the possibility of an underlying dynamic mutation.
Tawil
R
R
Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Forrester
J
J
Griggs
R C
RC
Mendell
J
J
Kissel
J
J
McDermott
M
M
King
W
W
Weiffenbach
B
B
Figlewicz
D
D
D000293:Adolescent; D000328:Adult; D015139:Blotting, Southern; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D008297:Male; D009136:Muscular Dystrophies / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D012720:Severity of Illness Index