caa a22 4500 445364629 CHVBK 20180317142926.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s10048-011-0281-x doi (NATIONALLICENCE)springer-10.1007/s10048-011-0281-x Ataxia with oculomotor apraxia type1 (AOA1): novel and recurrent aprataxin mutations, coenzyme Q10 analyses, and clinical findings in Italian patients [Elektronische Daten] [Barbara Castellotti, Caterina Mariotti, Marco Rimoldi, Roberto Fancellu, Massimo Plumari, Sara Caimi, Graziella Uziel, Nardo Nardocci, Isabella Moroni, Giovanna Zorzi, Davide Pareyson, Daniela Di Bella, Stefano Di Donato, Franco Taroni, Cinzia Gellera] Ataxia with oculomotor apraxia type1 (AOA1, MIM 208920) is a rare autosomal recessive disease caused by mutations in the APTX gene. We screened a cohort of 204 patients with cerebellar ataxia and 52 patients with early-onset isolated chorea. APTX gene mutations were found in 13 ataxic patients (6%). Eleven patients were homozygous for the known p.W279X, p.W279R, and p.P206L mutations. Three novel APTX mutations were identified: c.477delC (p.I159fsX171), c.C541T (p.Q181X), and c.C916T (p.R306X). Expression of mutated proteins in lymphocytes from these patients was greatly decreased. No mutations were identified in subjects with isolated chorea. Two heterozygous APTX sequence variants (p.L248M and p.D185E) were found in six families with ataxic phenotype. Analyses of coenzyme Q10 in muscle, fibroblasts, and plasma demonstrated normal levels of coenzyme in five of six mutated subjects. The clinical phenotype was homogeneous, irrespectively of the type and location of the APTX mutation, and it was mainly characterized by early-onset cerebellar signs, sensory neuropathy, cognitive decline, and oculomotor deficits. Three cases had slightly raised alpha-fetoprotein. Our survey describes one of the largest series of AOA1 patients and contributes in defining clinical, molecular, and biochemical characteristics of this rare hereditary neurological condition. Springer-Verlag, 2011 Aprataxin nationallicence APTX nationallicence Oculomotor apraxia nationallicence Recessive ataxia nationallicence Castellotti Barbara SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut Mariotti Caterina SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut Rimoldi Marco SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut Fancellu Roberto SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut Plumari Massimo SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut Caimi Sara SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut Uziel Graziella Child Neurology Department, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut Nardocci Nardo Child Neurology Department, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut Moroni Isabella Child Neurology Department, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut Zorzi Giovanna Child Neurology Department, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut Pareyson Davide SOSD Central and Peripheral Degenerative Neuropathies, Department of Clinical Neurosciences, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut Di Bella Daniela SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut Di Donato Stefano SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut Taroni Franco SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut Gellera Cinzia SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut neurogenetics Springer-Verlag 12/3(2011-08-01), 193-201 1364-6745 12:3<193 2011 12 10048 https://doi.org/10.1007/s10048-011-0281-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10048-011-0281-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Castellotti Barbara SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut NATIONALLICENCE 700 1- Mariotti Caterina SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut NATIONALLICENCE 700 1- Rimoldi Marco SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut NATIONALLICENCE 700 1- Fancellu Roberto SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut NATIONALLICENCE 700 1- Plumari Massimo SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut NATIONALLICENCE 700 1- Caimi Sara SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut NATIONALLICENCE 700 1- Uziel Graziella Child Neurology Department, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut NATIONALLICENCE 700 1- Nardocci Nardo Child Neurology Department, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut NATIONALLICENCE 700 1- Moroni Isabella Child Neurology Department, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut NATIONALLICENCE 700 1- Zorzi Giovanna Child Neurology Department, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut NATIONALLICENCE 700 1- Pareyson Davide SOSD Central and Peripheral Degenerative Neuropathies, Department of Clinical Neurosciences, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut NATIONALLICENCE 700 1- Di Bella Daniela SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut NATIONALLICENCE 700 1- Di Donato Stefano SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut NATIONALLICENCE 700 1- Taroni Franco SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut NATIONALLICENCE 700 1- Gellera Cinzia SOSD Genetics of Neurodegenerative and Metabolic Diseases, Fondazione-IRCCS, Istituto Neurologico "Carlo Besta”, via Celoria11, 20133, Milan, Italy aut NATIONALLICENCE 773 0- neurogenetics Springer-Verlag 12/3(2011-08-01), 193-201 1364-6745 12:3<193 2011 12 10048 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer