Identification of three novel frameshift mutations in patients with Friedreich's ataxia

• Published in: Journal of medical genetics Vol. 37; no. 11; pp. e38 - 38
• Main Authors: POOK, MARK A, AL-MAHDAWI, SAHAR A H, THOMAS, NEIL H, APPLETON, RICHARD, NORMAN, ANDREW, MOUNTFORD, ROGER, CHAMBERLAIN, SUSAN
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.11.2000; BMJ Publishing Group LTD; BMJ Group
• Subjects: Adolescent; Age; Age of Onset; Ataxia; Base Sequence; Cardiomyopathy; Child; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA - genetics; DNA Mutational Analysis; Electronic Letters; Family Health; Female; Frameshift Mutation; Frataxin; Friedreich Ataxia - genetics; Genes; Genotype & phenotype; Humans; Iron-Binding Proteins; Male; Mutation; Patients; Pedigree; Phosphotransferases (Alcohol Group Acceptor) - genetics; Polymorphism, Single-Stranded Conformational; Proteins; Sequence Deletion
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.37.11.e38

From a functional view, the 137delT and L106X mutations are expected to produce the same species of truncated frataxin protein and may give rise to a similar disease phenotype, depending on the size of the GAA expansion in the second allele. [...]although still of a young age, patient 1 who harbours the 137delT mutation and a 500 GAA repeat expansion already has signs of severe FRDA disease, resembling that of the two French patients who have the L106X mutation and GAA repeat sizes of 700 and 733, respectively. 9 The other two frameshift mutations described in this study, 202GTCA->TTG and 340del13, add a further complexity to both the positioning and the type of frataxin mutations identified so far. 202GTCA->TTG is the first mutation to be identified in exon 2 of the frataxin gene, and thereby shows that there is now at least one mutation in each of the five main frataxin exons.