Emil Ygland1, Franco Taroni2, Cinzia Gellera2, Serena Caldarazzo2, Morten Duno3, Maria Soller4, Andreas Puschmann5. 1. Department of Neurology, Skåne University Hospital, Lund, Sweden; Department of Neurology, Clinical Sciences, Lund University, Lund, Sweden. 2. Unit of Genetics of Neurodegenerative and Metabolic Disease, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. 3. Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 4. Department of Clinical Genetics, Skåne University Hospital, University and Regional Laboratories, Lund University, Lund, Sweden. 5. Department of Neurology, Skåne University Hospital, Lund, Sweden; Department of Neurology, Clinical Sciences, Lund University, Lund, Sweden. Electronic address: Andreas.Puschmann@med.lu.se.
Abstract
BACKGROUND: Compound heterozygosity for a trinucleotide repeat expansion and a point mutation in the FXN gene is a rare cause of Friedreich ataxia (FRDA). METHODS: We identified three Swedish FRDA patients with an FXN p.R165P missense mutation and compared their clinical features with six homozygote trinucleotide repeat expansion carriers. Patients were assessed clinically. Trinucleotide expansion length was determined and lymphocyte frataxin levels measured. RESULTS: p.R165P mutation carriers became wheelchair bound early, but had retained reflexes, better arm function, milder dysarthria, and were more independent in activities of daily living. One p.R165P mutation carrier developed psychosis. Frataxin levels were higher than in homozygous trinucleotide expansion patients. One patient with homozygous trinucleotide repeat expansions and comorbid hemochromatosis had more severe FRDA symptoms than his sibling without hemochromatosis. CONCLUSION: p.R165P patients progress to a less disabling disease state than typical FRDA. Comorbid hemochromatosis may worsen FRDA symptoms through additive effects on iron metabolism.
BACKGROUND: Compound heterozygosity for a trinucleotide repeat expansion and a point mutation in the FXN gene is a rare cause of Friedreich ataxia (FRDA). METHODS: We identified three Swedish FRDA patients with an FXN p.R165P missense mutation and compared their clinical features with six homozygote trinucleotide repeat expansion carriers. Patients were assessed clinically. Trinucleotide expansion length was determined and lymphocyte frataxin levels measured. RESULTS: p.R165P mutation carriers became wheelchair bound early, but had retained reflexes, better arm function, milder dysarthria, and were more independent in activities of daily living. One p.R165P mutation carrier developed psychosis. Frataxin levels were higher than in homozygous trinucleotide expansion patients. One patient with homozygous trinucleotide repeat expansions and comorbid hemochromatosis had more severe FRDA symptoms than his sibling without hemochromatosis. CONCLUSION: p.R165P patients progress to a less disabling disease state than typical FRDA. Comorbid hemochromatosis may worsen FRDA symptoms through additive effects on iron metabolism.
Authors: Josef Davidsson; Andreas Puschmann; Ulf Tedgård; David Bryder; Lars Nilsson; Jörg Cammenga Journal: Leukemia Date: 2018-02-25 Impact factor: 11.528
Authors: Emil Ygland; Danielle van Westen; Elisabet Englund; Rosa Rademakers; Zbigniew K Wszolek; Karin Nilsson; Christer Nilsson; Maria Landqvist Waldö; Irina Alafuzoff; Oskar Hansson; Lars Gustafson; Andreas Puschmann Journal: Alzheimers Res Ther Date: 2018-01-09 Impact factor: 6.982