title: Screening of CHCHD10 in a French cohort confirms the involvement of this gene in frontotemporal dementia with amyotrophic lateral sclerosis patients.
abstract: Mutations in the CHCHD10 gene have been recently identified in a large family with a complex phenotype variably associating frontotemporal dementia (FTD) with amyotrophic lateral sclerosis (ALS), cerebellar ataxia, myopathy, and hearing impairment. CHCHD10 encodes a protein located in the mitochondrial intermembrane space and is likely involved in mitochondrial genome stability and maintenance of cristae junctions. However, the exact contribution of CHCHD10 in FTD and ALS diseases spectrum remains unknown. In this study, we evaluated the frequency of CHCHD10 mutations in 115 patients with FTD and FTD-ALS phenotypes. We identified 2 heterozygous variants in 3 unrelated probands presenting FTD and ALS, characterized by early and predominant bulbar symptoms. This study demonstrates the implication of CHCHD10 in FTD and ALS spectrum. Although the frequency of mutations is low in this series (2.6%), our work suggests that CHCHD10 mutations should be searched particularly when bulbar symptoms are present at onset.
authors.affiliation: IRCAN, UMR CNRS 7284/INSERM U1081/UNS, School of Medicine, Nice Sophia-Antipolis University, Nice, France; Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, Nice, France.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Chaussenot
authors.affiliation: Sorbonne Université, UPMC University Paris 06, UM75, Inserm U1127, Cnrs UMR7225, Institut du Cerveau et de la Moelle épinière (ICM), Paris, France; National Reference Centre on Rare Dementias, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Le Ber
authors.affiliation: IRCAN, UMR CNRS 7284/INSERM U1081/UNS, School of Medicine, Nice Sophia-Antipolis University, Nice, France; Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, Nice, France.
authors.forename: Samira
authors.initials: S
authors.lastname: Ait-El-Mkadem
authors.affiliation: Sorbonne Université, UPMC University Paris 06, UM75, Inserm U1127, Cnrs UMR7225, Institut du Cerveau et de la Moelle épinière (ICM), Paris, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Camuzat
authors.affiliation: Sorbonne Université, UPMC University Paris 06, UM75, Inserm U1127, Cnrs UMR7225, Institut du Cerveau et de la Moelle épinière (ICM), Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: de Septenville
authors.affiliation: IRCAN, UMR CNRS 7284/INSERM U1081/UNS, School of Medicine, Nice Sophia-Antipolis University, Nice, France; Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, Nice, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bannwarth
authors.affiliation: IRCAN, UMR CNRS 7284/INSERM U1081/UNS, School of Medicine, Nice Sophia-Antipolis University, Nice, France.
authors.forename: Emmanuelle C
authors.initials: EC
authors.lastname: Genin
authors.affiliation: UMR7592 CNRS, Jacques Monod Institute, Paris Diderot University, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Serre
authors.affiliation: IRCAN, UMR CNRS 7284/INSERM U1081/UNS, School of Medicine, Nice Sophia-Antipolis University, Nice, France; Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, Nice, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Augé
authors.affiliation: Sorbonne Université, UPMC University Paris 06, UM75, Inserm U1127, Cnrs UMR7225, Institut du Cerveau et de la Moelle épinière (ICM), Paris, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.affiliation: Department of Neurology, Timone Hospital, Marseille Teaching Hospital, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Pouget
authors.affiliation: IRCAN, UMR CNRS 7284/INSERM U1081/UNS, School of Medicine, Nice Sophia-Antipolis University, Nice, France; Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, Nice, France. Electronic address: paquis@hermes.unice.fr.
authors.forename: Véronique
authors.initials: V
authors.lastname: Paquis-Flucklinger
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005602:France; D057180:Frontotemporal Dementia / Q000235:genetics*; D056726:Genetic Association Studies / Q000379:methods*; D042822:Genomic Instability / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010641:Phenotype
chemical_list: C554426:CHCHD10 protein, human; D024101:Mitochondrial Proteins
keywords: Amyotrophic lateral sclerosis (ALS); CHCHD10; Frontotemporal dementia (FTD); Frontotemporal lobar degeneration (FTLD); Mitochondrial disease