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
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