Abstract
Friedreich ataxia (FRDA) is the most common hereditary ataxia. It is an autosomal recessive disorder caused by mutations of the FXN gene, mainly the biallelic expansion of the (GAA)n repeats in its first intron. Heterozygous expansion/point mutations or deletions are rare; no patients with two point mutations or a point mutation/deletion have been described, suggesting that loss of the FXN gene product, frataxin, is lethal. This is why routine FRDA molecular diagnostics is focused on (GAA)n expansion analysis. Additional tests are considered only in cases of heterozygous expansion carriers and an atypical clinical picture. Analyses of the parent's carrier status, together with diagnostic tests, are performed in rare cases, and, because of that, we may underestimate the frequency of deletions. Even though FXN deletions are characterised as 'exquisitely rare,' we were able to identify one case (2.4 %) of a (GAA)n expansion/exonic deletion in a group of 41 probands. This was a patient with very early onset of disease with rapid progression of gait instability and hypertrophic cardiomyopathy. We compared the patient's clinical data to expansion/deletion carriers available in the literature and suggest that, in clinical practice, th...Continue Reading
References
Sep 1, 1981·Brain : a Journal of Neurology·A E Harding
Mar 8, 1996·Science·V CampuzanoM Pandolfo
Dec 1, 1996·Journal of Medical Genetics·J P WarnerD J Brock
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·M CosséeM Koenig
Aug 1, 1997·Human Molecular Genetics·L MonterminiS Cocozza
Sep 25, 1997·Human Molecular Genetics·V CampuzanoM Koenig
Sep 22, 1998·Prenatal Diagnosis·M Pandolfo, L Montermini
Jan 14, 2000·Journal of Medical Genetics·M B DelatyckiS M Forrest
Aug 22, 2002·Human Molecular Genetics·Rajesh SharmaSanjay I Bidichandani
Sep 2, 2004·European Journal of Human Genetics : EJHG·C H ZühlkeE Schwinger
Oct 15, 2008·Archives of Neurology·Massimo Pandolfo
Aug 3, 2010·Molecular Genetics and Metabolism·Eric C DeutschDavid R Lynch
Jun 10, 2011·Journal of the Neurological Sciences·Amy Y TsouDavid R Lynch
Mar 14, 2012·Archives of Neurology·Mathieu AnheimMichel Koenig
Jun 14, 2012·Genetic Testing and Molecular Biomarkers·Ans M W van den OuwelandDicky J J Halley