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Friedreich's ataxia in patients with FXN p.R165P point mutation

Ygland, E. LU ; Taroni, Franco; Gellera, Cinzia; Duno, M; Johnels, P. LU ; Soller, M. LU and Puschmann, A. LU (2012) 16th Congress of the European-Federation-of-Neurological-Societies (EFNS) In European Journal of Neurology 19(Suppl 1). p.727-727
Abstract
Introduction: Friedreich's ataxia (FRDA) is a hereditary disorder with progressive postural ataxia, dysarthria, neuropathy, muscle weakness and cardiomyopathy. Lack or malfunction of the protein frataxin due to mutations in the frataxin gene (FXN) is the cause of the disease. Most patients are homozygous for GAA trinucleotide expansions in FXN but disease can also be caused by heterozygosity for the expansion and a point mutation. Milder disease has been reported for some FRDA patients with missense mutations. Methods: We describe 3 FRDA patients, not previously reported, with the FXN p.R165P missense mutation and compared clinical features with 6 homozygous GAA expansion carriers. Patients were interviewed, examined clinically and... (More)
Introduction: Friedreich's ataxia (FRDA) is a hereditary disorder with progressive postural ataxia, dysarthria, neuropathy, muscle weakness and cardiomyopathy. Lack or malfunction of the protein frataxin due to mutations in the frataxin gene (FXN) is the cause of the disease. Most patients are homozygous for GAA trinucleotide expansions in FXN but disease can also be caused by heterozygosity for the expansion and a point mutation. Milder disease has been reported for some FRDA patients with missense mutations. Methods: We describe 3 FRDA patients, not previously reported, with the FXN p.R165P missense mutation and compared clinical features with 6 homozygous GAA expansion carriers. Patients were interviewed, examined clinically and assessed with FRDA rating scale (FARS). Blood was collected for reanalysis of GAA expansion length and for frataxin measurements. Results: Compared to patients homozygous for FXN GAA expansion, p.R165P mutation carriers had more wellpreserved upper limb function and deep tendon reflexes, considerably milder dysarthria, but possibly an increased occurrence of psychosis. p.R165P patients were more independent in activities of daily living, especially when correlated to disease duration. We found no difference in other clinical aspects or in GAA expansion length. One patient had severe FRDA symptoms and comorbid hemochromatosis, whereas his sibling without hemochromatosis had much milder disease. Refined analysis of GAA expansion length and frataxin levels are in progress. Conclusion: p.R165P FRDA patients appear to progress to a less disabling disease state than typical FRDA. We suggest additive effects of comorbid FRDA and hemochromatosis, due to synergistic abnormalities in iron metabolism. (Less)
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organization
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Contribution to journal
publication status
published
subject
keywords
frataxin, trinucleotide, protein, patient, point mutation, human, health care organization, Friedreich ataxia, hemochromatosis, missense mutation, dysarthria, clinical feature, mutation, sibling, disease duration, psychosis, tendon reflex, arm, gene, blood, rating scale, daily life activity, cardiomyopathy, iron metabolism, heterozygosity, muscle weakness, neuropathy, genetic disorder
in
European Journal of Neurology
volume
19
issue
Suppl 1
pages
1 pages
publisher
Wiley-Blackwell
conference name
16th Congress of the European-Federation-of-Neurological-Societies (EFNS)
ISSN
1351-5101
DOI
10.1111/j.1468-1331.2012.03889.x
language
English
LU publication?
yes
id
863fc641-3e30-43fb-9086-902b5cebb3b6
date added to LUP
2017-07-04 15:56:09
date last changed
2017-08-09 09:00:41
@misc{863fc641-3e30-43fb-9086-902b5cebb3b6,
  abstract     = {Introduction: Friedreich's ataxia (FRDA) is a hereditary disorder with progressive postural ataxia, dysarthria, neuropathy, muscle weakness and cardiomyopathy. Lack or malfunction of the protein frataxin due to mutations in the frataxin gene (FXN) is the cause of the disease. Most patients are homozygous for GAA trinucleotide expansions in FXN but disease can also be caused by heterozygosity for the expansion and a point mutation. Milder disease has been reported for some FRDA patients with missense mutations. Methods: We describe 3 FRDA patients, not previously reported, with the FXN p.R165P missense mutation and compared clinical features with 6 homozygous GAA expansion carriers. Patients were interviewed, examined clinically and assessed with FRDA rating scale (FARS). Blood was collected for reanalysis of GAA expansion length and for frataxin measurements. Results: Compared to patients homozygous for FXN GAA expansion, p.R165P mutation carriers had more wellpreserved upper limb function and deep tendon reflexes, considerably milder dysarthria, but possibly an increased occurrence of psychosis. p.R165P patients were more independent in activities of daily living, especially when correlated to disease duration. We found no difference in other clinical aspects or in GAA expansion length. One patient had severe FRDA symptoms and comorbid hemochromatosis, whereas his sibling without hemochromatosis had much milder disease. Refined analysis of GAA expansion length and frataxin levels are in progress. Conclusion: p.R165P FRDA patients appear to progress to a less disabling disease state than typical FRDA. We suggest additive effects of comorbid FRDA and hemochromatosis, due to synergistic abnormalities in iron metabolism.},
  author       = {Ygland, E. and Taroni, Franco and Gellera, Cinzia and Duno, M and Johnels, P. and Soller, M. and Puschmann, A.},
  issn         = {1351-5101},
  keyword      = {frataxin,trinucleotide,protein,patient,point mutation,human,health care organization,Friedreich ataxia,hemochromatosis,missense mutation,dysarthria,clinical feature,mutation,sibling,disease duration,psychosis,tendon reflex,arm,gene,blood,rating scale,daily life activity,cardiomyopathy,iron metabolism,heterozygosity,muscle weakness,neuropathy,genetic disorder},
  language     = {eng},
  month        = {09},
  note         = {Conference Abstract},
  number       = {Suppl 1},
  pages        = {727--727},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Neurology},
  title        = {Friedreich's ataxia in patients with FXN p.R165P point mutation},
  url          = {http://dx.doi.org/10.1111/j.1468-1331.2012.03889.x},
  volume       = {19},
  year         = {2012},
}