Please use this identifier to cite or link to this item:
Title: Somatic instability of the expanded GAA triplet-repeat sequence in Friedreich ataxia progresses throughout life
Authors: Pook, M A
De Biase, I
Ramussen, A
Monticelli, A
Al-Mahdawi, S
Cocozza, S
Bidichandani, S
Keywords: Friedreich ataxia;GAA triplet-repeat;somatic instability
Issue Date: 2007
Publisher: Elsevier
Citation: Genomics. 90 (1) 1-5
Abstract: Friedreich ataxia (FRDA) patients are homozygous for expanded GAA triplet-repeat alleles in the FXN gene. Primary neurodegeneration involving the dorsal root ganglia (DRG) results in progressive ataxia. While it is known that DRG are inherently sensitive to frataxin deficiency, recent observations also indicate that they show age-dependent, further expansion of the GAA triplet-repeat mutation. Whether somatic instability is progressive has not been systematically investigated in FRDA patients. Small pool PCR analysis of ~2300 individual molecules from tissues of an 18-week fetus, homozygous for expanded alleles, revealed very low levels of instability compared with adult-derived tissues (4.2% versus 30.6%, P<0.0001). Mutation load in blood samples from multiple patients and carriers increased significantly with age, ranging from 7.5% at 18-weeks gestation to 78.7% at 49y (R=0.91; P=0.0001). Therefore, somatic instability in FRDA occurs mostly after early embryonic development and progresses throughout life, lending further support to the role of postnatal somatic instability in disease pathogenesis.
ISSN: 0888-7543
Appears in Collections:Biological Sciences
Community Health and Public Health
Dept of Life Sciences Research Papers

Files in This Item:
File Description SizeFormat 
DeBiasePookGenomics2007.pdf777.8 kBAdobe PDFView/Open

Items in BURA are protected by copyright, with all rights reserved, unless otherwise indicated.