CHCH10 mutations in an Italian cohort of familial and sporadic amyotrophic lateral sclerosis patients.
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.
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: achio@usa.net.
Adriano
A
Chiò
Department of Neurological Rehabilitation, Fondazione Salvatore Maugeri, IRCCS, Istituto Scientifico di Milano, Milano, Italy.
Gabriele
G
Mora
Neurological Institute, Catholic University and I.C.O.M.M. Association for ALS Research, Rome, Italy.
Mario
M
Sabatelli
Department of Neurosciences, Ophthalmology, Genetics, Rehabilitation and Child Health, IRCCS Azienda Ospedaliero-Universitaria San Martino IST, University of Genoa, Italy.
Claudia
C
Caponnetto
Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Bryan J
BJ
Traynor
Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Janel O
JO
Johnson
Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Mike A
MA
Nalls
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.
Andrea
A
Calvo
ALS Center, 'Rita Levi Montalcini' Department of Neuroscience, Neurology II, University of Torino, Torino, Italy.
Cristina
C
Moglia
Department of Neurology, Azienda Universitario Ospedaliera di Cagliari and University of Cagliari, Cagliari, Italy.
Giuseppe
G
Borghero
Department of Neurological Sciences, Second University of Naples, Naples, Italy.
Maria Rosaria
MR
Monsurrò
ALS Clinical Research Center, Bio. Ne. C., University of Palermo, Palermo, Italy.
Vincenzo
V
La Bella
Neurorehabilitation Unit/ALS Center, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Mistretta, Mistretta, Italy.
Paolo
P
Volanti
Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy.
Isabella
I
Simone
Center for Diagnosis and Cure of Rare Diseases, Department of Neurology, IRCCS Institute of Neurological Sciences, Bologna, Italy.
Fabrizio
F
Salvi
Neurological Clinic, Marche Polytechnic University, Ancona, Italy.
Francesco O
FO
Logullo
Department of Neurology and Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Riva
R
Nilo
Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy.
Stefania
S
Battistini
Department of Neuroscience, S. Agostino-Estense Hospital, University of Modena, Modena, Italy.
Jessica
J
Mandrioli
Department of Neurology, Santa Chiara Hospital, Trento, Italy.
Raffaella
R
Tanel
Multiple Sclerosis Centre, ASL 8 Cagliari, University of Cagliari, Cagliari, Italy; Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Cagliari, Italy.
Maria Rita
MR
Murru
Department of Neurosciences, Ophthalmology, Genetics, Rehabilitation and Child Health, IRCCS Azienda Ospedaliero-Universitaria San Martino IST, University of Genoa, Italy.
Paola
P
Mandich
Institute of Medical Genetics, Catholic University of Sacred Heart, Rome, Italy.
Marcella
M
Zollino
Institute of Neurological Sciences, National Research Council, Mangone, Cosenza, Italy.
Francesca L
FL
Conforti
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.
Maura
M
Brunetti
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.
Marco
M
Barberis
Laboratory of Molecular Genetics, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy.
Gabriella
G
Restagno
Department of Laboratory Medicine, Medical Genetics, Niguarda Ca' Granda Hospital, Milan, Italy.
Silvana
S
Penco
NEuroMuscular Omnicenter, Serena Onlus Foundation, Milan, Italy.
Christian
C
Lunetta
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D057180:Frontotemporal Dementia; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation
C554426:CHCHD10 protein, human; D024101:Mitochondrial Proteins
Amyotrophic lateral sclerosis; CHCHD10; Familial; Sporadic