Clinical and allelic heterogeneity in a pediatric cohort of 11 patients carrying MFN2 mutation
Autor: | Chloé Di Meglio, Brigitte Chabrol, Mathieu Milh, Caroline Ovaert, Christophe Boulay, Nicolas Lévy, Nathalie Bonello-Palot |
---|---|
Přispěvatelé: | Centre de référence maladie rare Thalassémie, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire de Génétique Moléculaire [Hôpital de la Timone - APHM], Département de génétique médicale [Hôpital de la Timone - APHM], Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Adaptations et évolution des systèmes ostéomusculaires (AESO), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN), Service de pédiatrie et neurologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie Pédiatrique [Marseille], Hôpital de la Timone [CHU - APHM] (TIMONE), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Service de Neurologie Pédiatrique, Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine Pediatrics Pathology Subacute polyneuropathy GTP Phosphohydrolases Cohort Studies 0302 clinical medicine Charcot-Marie-Tooth Disease Spastic Family history Child medicine.diagnostic_test General Medicine Pedigree 3. Good health Phenotype Child Preschool Female Allelic heterogeneity medicine.medical_specialty Genotype Respiratory chain deficiency Mitochondrial Proteins 03 medical and health sciences Atrophy Developmental Neuroscience White matter lesion [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Charcot-Marie-Tooth (CMT) medicine Humans Optic atrophy Genetic Testing Allele Alleles Genetic testing Muscle biopsy business.industry Infant Membrane Proteins medicine.disease Neuropathy 030104 developmental biology Mitofusin 2 (MFN2) Pediatrics Perinatology and Child Health Histopathology Neurology (clinical) business 030217 neurology & neurosurgery |
Zdroj: | Brain and Development Brain and Development, Elsevier, 2016, 38 (5), pp.498-506. ⟨10.1016/j.braindev.2015.11.006⟩ Brain and Development, 2016, 38 (5), pp.498-506. ⟨10.1016/j.braindev.2015.11.006⟩ |
ISSN: | 0387-7604 |
Popis: | International audience; Introduction: The Mitofusin 2 gene (MFN2), which encodes a mitochondrial membrane protein, is known to be the first cause of autosomal dominant Charcot Marie Tooth disease type 2 (CMT2) with early onset. This gene is involved in typical CMT2A and in more atypical phenotypes as optic atrophy or spastic paraplegia. CMT2 refers to inherited axonal polyneuropathy, which associates progressive peripheral motor and sensory neuropathy, a family history consistent mainly with autosomal dominant inheritance, and normal nerve conduction velocities. Subjects: Between 1999 and 2012, the genetic diagnosis of MFN2 mutation was made in 11 children who were treated in our department for different neurological symptoms. All data including family and personal history data, results of standardized clinical and electrophysiology testing, brain magnetic resonance imaging (MRI), neuro-ophthalmic evaluation, muscle biopsy histopathology and molecular diagnosis were retrospectively analyzed. Results: Five different mutations were found in 6 unrelated families. Three of them have previously been described; the two remaining are new mutations: one of them related a new phenotype. Clinical signs appeared before the age of 6 years in more than half of the patients (54%). The motor deficit was predominant in 8 patients (72%). Two children presented an acute onset of disease that stabilized afterwards; the other children showed a more progressive deterioration that was managed symptomatically. Conclusion: This large pediatric study describes a great interfamilial and intrafamilial phenotypic variability. We recommend screening this gene in pediatric patient with chronic neurologic symptoms such as motor deficit or optic atrophy but also in acute neurologic deficiencies such as subacute polyradiculoneuritis. (C) 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. |
Databáze: | OpenAIRE |
Externí odkaz: |