title: Friedreich ataxia is not only a GAA repeats expansion disorder: implications for molecular testing and counselling.
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, the FXN deletion test should be taken into account in patients with early-onset, rapid progressive ataxia and severe scoliosis.
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17A, 01 211, Warsaw, Poland. dhoffman@wp.pl.|Institute of Genetics and Biotechnology, Warsaw University, Warsaw, Poland. dhoffman@wp.pl.
authors.forename: Dorota
authors.initials: D
authors.lastname: Hoffman-Zacharska
authors.affiliation: Clinic of Neurology, Institute of Mother and Child, Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Mazurczak
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17A, 01 211, Warsaw, Poland.|Institute of Genetics and Biotechnology, Warsaw University, Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Zajkowski
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17A, 01 211, Warsaw, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Tataj
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17A, 01 211, Warsaw, Poland.|Clinic of Neurology, Institute of Mother and Child, Warsaw, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Górka-Skoczylas
authors.affiliation: Department of Neurology, Polish Mother's Memorial Hospital-Research Institute, Łódź, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Połatyńska
authors.affiliation: Molecular Biology Unit, Department of Internal Diseases and Nephrodiabetology, Medical University of Łódz, Łódz, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Kępczyński
authors.affiliation: Department of Neurology, Polish Mother's Memorial Hospital-Research Institute, Łódź, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Stasiołek
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Kasprzaka 17A, 01 211, Warsaw, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Bal
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005260:Female; D005621:Friedreich Ataxia / Q000175:diagnosis* / Q000235:genetics; D005817:Genetic Counseling; D005820:Genetic Testing / Q000379:methods*; D006579:Heterozygote; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D017384:Sequence Deletion; D000096923:Frataxin
chemical_list: D033862:Iron-Binding Proteins; D000096923:Frataxin
keywords: Clinical heterogeneity; Deletions; Dynamic mutation; FXN gene; Friedreich ataxia; Molecular diagnostics