caa a22 4500 445364688 CHVBK 20180317142926.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s10048-011-0296-3 doi (NATIONALLICENCE)springer-10.1007/s10048-011-0296-3 A novel deletion-insertion mutation identified in exon 3 of FXN in two siblings with a severe Friedreich ataxia phenotype [Elektronische Daten] [Marguerite Evans-Galea, Louise Corben, Justin Hasell, Charles Galea, Michael Fahey, Desirée du Sart, Martin Delatycki] Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease most commonly caused by a GAA trinucleotide repeat expansion in the first intron of FXN, which reduces expression of the mitochondrial protein frataxin. Approximately 98% of individuals with FRDA are homozygous for GAA expansions, with the remaining 2% compound heterozygotes for a GAA expansion and a point mutation within FXN. Two siblings with early onset of symptoms experienced rapid loss of ambulation by 8 and 10years. Diagnostic testing for FRDA demonstrated one GAA repeat expansion of 1010 repeats and one non-expanded allele. Sequencing all five exons of FXN identified a novel deletion-insertion mutation in exon 3 (c.371_376del6ins15), which results in a modified frataxin protein sequence at amino acid positions 124-127. Specifically, the amino acid sequence changes from DVSF to VHLEDT, increasing frataxin from 211 residues to 214. Using the known structure of human frataxin, a theoretical 3D model of the mutant protein was developed. In the event that the modified protein is expressed and stable, it is predicted that the acidic interface of frataxin, known to be involved in iron binding and interactions with the iron-sulphur cluster assembly factor IscU, would be impaired. Springer-Verlag, 2011 Friedreich ataxia nationallicence Mutation nationallicence Compound heterozygote nationallicence Frataxin nationallicence FXN nationallicence Neurodegenerative disease nationallicence Evans-Galea Marguerite Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Flemington Road, 3052, Parkville, Victoria, Australia aut Corben Louise Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Flemington Road, 3052, Parkville, Victoria, Australia aut Hasell Justin Molecular Genetics Laboratory, Victorian Clinical Genetics Services Pathology, Murdoch Childrens Research Institute, 3052, Parkville, Victoria, Australia aut Galea Charles Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, 3052, Parkville, Victoria, Australia aut Fahey Michael Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Flemington Road, 3052, Parkville, Victoria, Australia aut du Sart Desirée Molecular Genetics Laboratory, Victorian Clinical Genetics Services Pathology, Murdoch Childrens Research Institute, 3052, Parkville, Victoria, Australia aut Delatycki Martin Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Flemington Road, 3052, Parkville, Victoria, Australia aut neurogenetics Springer-Verlag 12/4(2011-11-01), 307-313 1364-6745 12:4<307 2011 12 10048 https://doi.org/10.1007/s10048-011-0296-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10048-011-0296-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Evans-Galea Marguerite Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Flemington Road, 3052, Parkville, Victoria, Australia aut NATIONALLICENCE 700 1- Corben Louise Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Flemington Road, 3052, Parkville, Victoria, Australia aut NATIONALLICENCE 700 1- Hasell Justin Molecular Genetics Laboratory, Victorian Clinical Genetics Services Pathology, Murdoch Childrens Research Institute, 3052, Parkville, Victoria, Australia aut NATIONALLICENCE 700 1- Galea Charles Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, 3052, Parkville, Victoria, Australia aut NATIONALLICENCE 700 1- Fahey Michael Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Flemington Road, 3052, Parkville, Victoria, Australia aut NATIONALLICENCE 700 1- du Sart Desirée Molecular Genetics Laboratory, Victorian Clinical Genetics Services Pathology, Murdoch Childrens Research Institute, 3052, Parkville, Victoria, Australia aut NATIONALLICENCE 700 1- Delatycki Martin Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Flemington Road, 3052, Parkville, Victoria, Australia aut NATIONALLICENCE 773 0- neurogenetics Springer-Verlag 12/4(2011-11-01), 307-313 1364-6745 12:4<307 2011 12 10048 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer