title: Two novel cases of compound heterozygous mutations in mitofusin2: Finding out the inheritance.
abstract: MFN2 is the major gene involved in the axonal form of Charcot-Marie-Tooth disease. It usually has an autosomal dominant pattern of inheritance, but a few cases of homozygous or compound heterozygous mutations have been described. These patients usually present an earlier onset, more severe phenotype and their inheritance pattern can span from autosomal recessive to semidominant. Here we report two unrelated patients carrying two compound heterozygous MFN2 mutations. Both present a pure axonal neuropathy without any additional features. The first patient presents a mild clinical phenotype with onset in the 2nd decade, while the second patient shows a severe, early onset phenotype with loss of independent ambulation. Only a careful clinical examination as well as neurophysiological and genetic studies allowed us to establish the role and the transmission pattern of the identified variants. We discuss practical consequences of this finding in genetic counseling.
authors.affiliation: Dept. of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, Section of Medical Genetics, University of Genoa, 16132 Genoa, Italy. Electronic address: ageroldi@hotmail.com.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Geroldi
authors.affiliation: UOC Medicina Interna Universitaria "Cesare Frugoni", Centro Sovraziendale Malattie Rare, AOU Consorziale Policlinico Giovanni XXIII, Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Lastella
authors.affiliation: UOC Laboratorio di Genetica Medica Universitaria, D.A.I. di Patologia Diagnostica, Bioimmagini e Sanità Pubblica, AOU Consorziale Policlinico di Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Patruno
authors.affiliation: Dept. of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, Section of Medical Genetics, University of Genoa, 16132 Genoa, Italy; COU Medical Genetics, IRCCS AOU San Martino IST - Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Gotta
authors.affiliation: UOC Laboratorio di Genetica Medica Universitaria, D.A.I. di Patologia Diagnostica, Bioimmagini e Sanità Pubblica, AOU Consorziale Policlinico di Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Resta
authors.affiliation: Neurological Unit, Dept of Neuroscience, University Hospital "Santa Maria della Misericordia", Udine, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Devigili
authors.affiliation: UOC Medicina Interna Universitaria "Cesare Frugoni", Centro Sovraziendale Malattie Rare, AOU Consorziale Policlinico Giovanni XXIII, Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Sabbà
authors.affiliation: COU Medical Genetics, IRCCS AOU San Martino IST - Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Gulli
authors.affiliation: Dept. of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, Section of Medical Genetics, University of Genoa, 16132 Genoa, Italy; COU Medical Genetics, IRCCS AOU San Martino IST - Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Merit
authors.initials: M
authors.lastname: Lamp
authors.affiliation: Dept. of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, Section of Medical Genetics, University of Genoa, 16132 Genoa, Italy; COU Medical Genetics, IRCCS AOU San Martino IST - Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Origone
authors.affiliation: Dept. of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, Section of Medical Genetics, University of Genoa, 16132 Genoa, Italy; COU Medical Genetics, IRCCS AOU San Martino IST - Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Mandich
authors.affiliation: Dept. of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, Section of Medical Genetics, University of Genoa, 16132 Genoa, Italy; COU Medical Genetics, IRCCS AOU San Martino IST - Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Bellone
mesh_terms: D000293:Adolescent; D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D024101:Mitochondrial Proteins / Q000235:genetics*; D010375:Pedigree
chemical_list: D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human
keywords: CMT2; Compound heterozygosity; Genetic counseling; Inheritance; MFN2