CHCH10 mutations in an Italian cohort of familial and sporadic amyotrophic lateral sclerosis patients

Adriano Chiò; Gabriele Mora; Mario Sabatelli; Claudia Caponnetto; Bryan J Traynor; Janel O Johnson; Mike A Nalls; Andrea Calvo; Cristina Moglia; Giuseppe Borghero; Maria Rosaria Monsurrò; Vincenzo La Bella; Paolo Volanti; Isabella Simone; Fabrizio Salvi; Francesco O Logullo; Riva Nilo; Stefania Battistini; Jessica Mandrioli; Raffaella Tanel; Maria Rita Murru; Paola Mandich; Marcella Zollino; Francesca L Conforti; ITALSGEN Consortium; Maura Brunetti; Marco Barberis; Gabriella Restagno; Silvana Penco; Christian Lunetta

doi:10.1016/j.neurobiolaging.2015.01.017

CHCH10 mutations in an Italian cohort of familial and sporadic amyotrophic lateral sclerosis patients

Neurobiol Aging. 2015 Apr;36(4):1767.e3-1767.e6. doi: 10.1016/j.neurobiolaging.2015.01.017. Epub 2015 Jan 28.

Authors

Adriano Chiò¹, Gabriele Mora², Mario Sabatelli³, Claudia Caponnetto⁴, Bryan J Traynor⁵, Janel O Johnson⁵, Mike A Nalls⁶, Andrea Calvo⁷, Cristina Moglia⁸, Giuseppe Borghero⁹, Maria Rosaria Monsurrò¹⁰, Vincenzo La Bella¹¹, Paolo Volanti¹², Isabella Simone¹³, Fabrizio Salvi¹⁴, Francesco O Logullo¹⁵, Riva Nilo¹⁶, Stefania Battistini¹⁷, Jessica Mandrioli¹⁸, Raffaella Tanel¹⁹, Maria Rita Murru²⁰, Paola Mandich⁴, Marcella Zollino²¹, Francesca L Conforti²²; ITALSGEN Consortium; Maura Brunetti²³, Marco Barberis²³, Gabriella Restagno²⁴, Silvana Penco²⁵, Christian Lunetta²⁶

Affiliations

¹ ALS Center, 'Rita Levi Montalcini' Department of Neuroscience, Neurology II, University of Torino, Torino, Italy; Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy. Electronic address: [email protected].
² Department of Neurological Rehabilitation, Fondazione Salvatore Maugeri, IRCCS, Istituto Scientifico di Milano, Milano, Italy.
³ Neurological Institute, Catholic University and I.C.O.M.M. Association for ALS Research, Rome, Italy.
⁴ Department of Neurosciences, Ophthalmology, Genetics, Rehabilitation and Child Health, IRCCS Azienda Ospedaliero-Universitaria San Martino IST, University of Genoa, Italy.
⁵ Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
⁶ Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
⁷ ALS Center, 'Rita Levi Montalcini' Department of Neuroscience, Neurology II, University of Torino, Torino, Italy; Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy.
⁸ ALS Center, 'Rita Levi Montalcini' Department of Neuroscience, Neurology II, University of Torino, Torino, Italy.
⁹ Department of Neurology, Azienda Universitario Ospedaliera di Cagliari and University of Cagliari, Cagliari, Italy.
¹⁰ Department of Neurological Sciences, Second University of Naples, Naples, Italy.
¹¹ ALS Clinical Research Center, Bio. Ne. C., University of Palermo, Palermo, Italy.
¹² Neurorehabilitation Unit/ALS Center, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Mistretta, Mistretta, Italy.
¹³ Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy.
¹⁴ Center for Diagnosis and Cure of Rare Diseases, Department of Neurology, IRCCS Institute of Neurological Sciences, Bologna, Italy.
¹⁵ Neurological Clinic, Marche Polytechnic University, Ancona, Italy.
¹⁶ Department of Neurology and Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Scientific Institute, Milan, Italy.
¹⁷ Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy.
¹⁸ Department of Neuroscience, S. Agostino-Estense Hospital, University of Modena, Modena, Italy.
¹⁹ Department of Neurology, Santa Chiara Hospital, Trento, Italy.
²⁰ Multiple Sclerosis Centre, ASL 8 Cagliari, University of Cagliari, Cagliari, Italy; Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Cagliari, Italy.
²¹ Institute of Medical Genetics, Catholic University of Sacred Heart, Rome, Italy.
²² Institute of Neurological Sciences, National Research Council, Mangone, Cosenza, Italy.
²³ ALS Center, 'Rita Levi Montalcini' Department of Neuroscience, Neurology II, University of Torino, Torino, Italy; Laboratory of Molecular Genetics, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy.
²⁴ Laboratory of Molecular Genetics, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy.
²⁵ Department of Laboratory Medicine, Medical Genetics, Niguarda Ca' Granda Hospital, Milan, Italy.
²⁶ NEuroMuscular Omnicenter, Serena Onlus Foundation, Milan, Italy.

PMID: 25726362
PMCID: PMC4380794
DOI: 10.1016/j.neurobiolaging.2015.01.017

Abstract

Mutations in CHCHD10 have recently been described as a cause of frontotemporal dementia (FTD) comorbid with amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the frequency and clinical characteristics of CHCHD10 mutations in Italian patients diagnosed with familial (n = 64) and apparently sporadic ALS (n = 224). Three apparently sporadic patients were found to carry c.100C>T (p.Pro34Ser) heterozygous variant in the exon 2 of CHCHD10. This mutation had been previously described in 2 unrelated French patients with FTD-ALS. However, our patients had a typical ALS, without evidence of FTD, cerebellar or extrapyramidal signs, or sensorineural deficits. We confirm that CHCHD10 mutations account for ∼ 1% of Italian ALS patients and are a cause of disease in subjects without dementia or other atypical clinical signs.

Keywords: Amyotrophic lateral sclerosis; CHCHD10; Familial; Sporadic.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Amyotrophic Lateral Sclerosis / genetics*
Cohort Studies
Female
Frontotemporal Dementia
Genetic Association Studies*
Genetic Predisposition to Disease / genetics*
Humans
Italy
Male
Middle Aged
Mitochondrial Proteins / genetics*
Mutation*

CHCH10 mutations in an Italian cohort of familial and sporadic amyotrophic lateral sclerosis patients

Authors

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Abstract

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