Fragile X-associated tremor/ataxia syndrome in sisters related to X-inactivation.
Fragile X tremor/ataxia syndrome (FXTAS) is a recently described condition consisting of tremor, ataxia, parkinsonism, and executive dysfunction, presenting predominantly in male carriers of a fragile X mental retardation 1 premutation. In this report, we present premutation carrier sisters in whom severity of clinical signs correlated with a molecular pattern of X-inactivation favoring higher expression of the premutation allele. In these women with a common genetic background, we suggest that symptom severity may be dictated by X-inactivation, and thus a higher percentage of cells producing the premutation-containing mRNA result in increased toxicity and disease.
Berry-Kravis
Elizabeth
E
Department of Pediatrics, Rush University Medical Center, 1275 West Harrison Street, Suite 718, Chicago, IL 60612, USA. elizabeth_m_berry-kravis@rush.edu
Potanos
Kristina
K
Weinberg
Dahlia
D
Zhou
Lili
L
Goetz
Christopher G
CG
D000368:Aged; D000369:Aged, 80 and over; D001259:Ataxia / Q000150:complications*; D001931:Brain Mapping; D041321:Chromosomes, Human, X / Q000235:genetics*; D019175:DNA Methylation; D004303:Dosage Compensation, Genetic; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000150:complications* / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D035781:Siblings; D014202:Tremor / Q000150:complications*
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human