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.
Clinical use of frataxin measurement in a patient with a novel deletion in the FXN gene / Sacca', Francesco; Marsili, A; Puorro, G; Antenora, A; Pane, C; Tessa, A; Scoppettuolo, P; Nesti, C; BRESCIA MORRA, Vincenzo; DE MICHELE, Giuseppe; Santorelli, Fm; Filla, Alessandro. - In: JOURNAL OF NEUROLOGY. - ISSN 0340-5354. - STAMPA. - 260:(2013), pp. 1116-1121. [10.1007/s00415-012-6770-5]
Clinical use of frataxin measurement in a patient with a novel deletion in the FXN gene.
SACCA', FRANCESCO;BRESCIA MORRA, VINCENZO;DE MICHELE, GIUSEPPE;FILLA, ALESSANDRO
2013
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.File | Dimensione | Formato | |
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