title: Autosomal recessive MFN2-related Charcot-Marie-Tooth disease with diaphragmatic weakness: Case report and literature review.
abstract: Pathogenic variants in the mitofusin 2 gene (MFN2) are the most common cause of autosomal dominant Charcot-Marie-Tooth (CMT2) disease, which is typically characterized by axonal sensorimotor neuropathy. We report on a 7-month-old white female with hypotonia, motor delay, distal weakness, and motor/sensory axonal neuropathy in which next-generation sequencing analysis identified compound heterozygous pathogenic variants (c.2054_2069_1170del and c.392A>G) in MFN2. A review of the literature reveals that sporadic and familial cases of compound heterozygous or homozygous pathogenic MFN2 variants have been infrequently described, which indicates that MFN2 can also be inherited in a recessive manner. This case highlights several clinical findings not typically associated with MFN2 pathogenic variants, including young age of onset and rapidly progressing diaphragmatic paresis that necessitated tracheostomy and mechanical ventilation, and adds to the growing list of features identified in autosomal recessive MFN2-related CMT2. Our patient with MFN2-related CMT2 expands the clinical and mutational spectrum of individuals with autosomal recessive CMT2 and identifies a new clinical feature that warrants further observation. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Invitae Corporation, San Francisco, California.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Tan
authors.affiliation: Invitae Corporation, San Francisco, California.
authors.forename: Marina
authors.initials: M
authors.lastname: Rabideau
authors.affiliation: Department of Pediatrics, Levine Children's Hospital/Carolinas Healthcare System, Charlotte, North Carolina.
authors.forename: Amy
authors.initials: A
authors.lastname: Blevins
authors.affiliation: Invitae Corporation, San Francisco, California.
authors.forename: Marjorie Jody
authors.initials: MJ
authors.lastname: Westbrook
authors.affiliation: Invitae Corporation, San Francisco, California.
authors.forename: Tali
authors.initials: T
authors.lastname: Ekstein
authors.affiliation: Invitae Corporation, San Francisco, California.
authors.forename: Keith
authors.initials: K
authors.lastname: Nykamp
authors.affiliation: Invitae Corporation, San Francisco, California.|Department of Laboratory Medicine, University of California San Francisco, San Francisco, California.
authors.forename: Anne
authors.initials: A
authors.lastname: Deucher
authors.affiliation: Department of Pediatrics, Levine Children's Hospital/Carolinas Healthcare System, Charlotte, North Carolina.
authors.forename: Amy
authors.initials: A
authors.lastname: Harper
authors.affiliation: Department of Pediatrics, Levine Children's Hospital/Carolinas Healthcare System, Charlotte, North Carolina.
authors.forename: Laurie
authors.initials: L
authors.lastname: Demmer
mesh_terms: D000483:Alleles; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis* / Q000235:genetics*; D003964:Diaphragm / Q000503:physiopathology*; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D005808:Genes, Recessive; D056726:Genetic Association Studies; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D024101:Mitochondrial Proteins / Q000235:genetics*; D018908:Muscle Weakness / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human
keywords: CMT2; Charcot-Marie-Tooth disease; mitofusin 2