title: Clinical use of frataxin measurement in a patient with a novel deletion in the FXN gene.
abstract: Friedreich ataxia (FRDA) is caused by a GAA expansion in the first intron of the FXN gene, which encodes frataxin. Four percent of patients harbor a point mutation on one allele and a GAA expansion on the other. We studied an Italian patient presenting with symptoms suggestive of FRDA, and carrying a single expanded 850 GAA allele. As a second diagnostic step, frataxin was measured in peripheral blood mononuclear cells, and proved to be in the pathological range (2.95 pg/μg total protein, 12.7 % of control levels). Subsequent sequencing revealed a novel deletion in exon 5a (c.572delC) which predicted a frameshift at codon 191 and a premature truncation of the protein at codon 194 (p.T191IfsX194). FXN/mRNA expression was reduced to 69.2 % of control levels. Clinical phenotype was atypical with absent dysarthria, and rapid disease progression. L-Buthionine-sulphoximine treatment of the proband's lymphoblasts showed a severe phenotype as compared to classic FRDA.
authors.affiliation: Department of Neurological Sciences, University Federico II, Via Pansini 5, 80131 Naples, NA, Italy. francesco.sacca@unina.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Saccà
authors.forename: Angela
authors.initials: A
authors.lastname: Marsili
authors.forename: Giorgia
authors.initials: G
authors.lastname: Puorro
authors.forename: Antonella
authors.initials: A
authors.lastname: Antenora
authors.forename: Chiara
authors.initials: C
authors.lastname: Pane
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tessa
authors.forename: Pasquale
authors.initials: P
authors.lastname: Scoppettuolo
authors.forename: Claudia
authors.initials: C
authors.lastname: Nesti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Brescia Morra
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Michele
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Filla
mesh_terms: D000704:Analysis of Variance; D000963:Antimetabolites / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002461:Cell Line, Transformed; D005192:Family Health; D005260:Female; D005621:Friedreich Ataxia / Q000235:genetics* / Q000473:pathology; D005820:Genetic Testing; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics*; D012720:Severity of Illness Index; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D055815:Young Adult; D000096923:Frataxin
chemical_list: D000963:Antimetabolites; D019328:Buthionine Sulfoximine; D033862:Iron-Binding Proteins; D012333:RNA, Messenger; D000096923:Frataxin