title: A novel AIFM1 mutation expands the phenotype to an infantile motor neuron disease.
abstract: AIFM1 is a gene located on the X chromosome, coding for AIF (Apoptosis-Inducing Factor), a mitochondrial flavoprotein involved in caspase-independent cell death. AIFM1 mutations have been associated with different clinical phenotypes: a severe infantile encephalopathy with combined oxidative phosphorylation deficiency and the Cowchock syndrome, an X-linked Charcot-Marie-Tooth disease (CMTX4) with axonal sensorimotor neuropathy, deafness and cognitive impairment. In two male cousins with early-onset mitochondrial encephalopathy and cytochrome c oxidase (COX) deficiency, we identified a novel AIFM1 mutation. Muscle biopsies and electromyography in both patients showed signs of severe denervation. Our patients manifested a phenotype that included signs of both cortical and motor neuron involvement. These observations emphasize the role of AIF in the development and function of neurons.
authors.affiliation: Neuromuscular and Neurodegenerative Diseases Unit, Children Research Hospital Bambino Gesù, Rome, Italy.
authors.forename: Daria
authors.identifier: http://orcid.org/0000-0003-3607-8523
authors.initials: D
authors.lastname: Diodato
authors.affiliation: Neuromuscular and Neurodegenerative Diseases Unit, Children Research Hospital Bambino Gesù, Rome, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Tasca
authors.affiliation: Neuromuscular and Neurodegenerative Diseases Unit, Children Research Hospital Bambino Gesù, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Verrigni
authors.affiliation: Neuromuscular and Neurodegenerative Diseases Unit, Children Research Hospital Bambino Gesù, Rome, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: D'Amico
authors.affiliation: Neuromuscular and Neurodegenerative Diseases Unit, Children Research Hospital Bambino Gesù, Rome, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Rizza
authors.affiliation: Neuromuscular and Neurodegenerative Diseases Unit, Children Research Hospital Bambino Gesù, Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Tozzi
authors.affiliation: Division of Metabolism, Children Research Hospital Bambino Gesù, Rome, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Martinelli
authors.affiliation: Neuromuscular and Neurodegenerative Diseases Unit, Children Research Hospital Bambino Gesù, Rome, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Verardo
authors.affiliation: Molecular Neurogenetics Unit, Foundation IRCCS Neurological Institute C, Besta, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Invernizzi
authors.affiliation: Molecular Neurogenetics Unit, Foundation IRCCS Neurological Institute C, Besta, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Nasca
authors.affiliation: Research Laboratories, Children Research Hospital Bambino Gesù, Rome, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Bellacchio
authors.affiliation: Molecular Neurogenetics Unit, Foundation IRCCS Neurological Institute C, Besta, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Ghezzi
authors.affiliation: Neuromuscular and Neurodegenerative Diseases Unit, Children Research Hospital Bambino Gesù, Rome, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Piemonte
authors.affiliation: Division of Metabolism, Children Research Hospital Bambino Gesù, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Dionisi-Vici
authors.affiliation: Neuromuscular and Neurodegenerative Diseases Unit, Children Research Hospital Bambino Gesù, Rome, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Carrozzo
authors.affiliation: Neuromuscular and Neurodegenerative Diseases Unit, Children Research Hospital Bambino Gesù, Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
mesh_terms: D000595:Amino Acid Sequence; D051033:Apoptosis Inducing Factor / Q000737:chemistry / Q000235:genetics*; D005190:Family; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D016472:Motor Neuron Disease / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D016415:Sequence Alignment
chemical_list: C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor