title: Molecular genetics of autosomal-recessive axonal Charcot-Marie-Tooth neuropathies.
abstract: Autosomal-recessive forms of Charcot-Marie-Tooth (ARCMT) account for less than 10% of the families with CMT. On the other hand, in countries with a high prevalence of consanguinity this mode of inheritance accounts, likely, for the vast majority of CMT phenotypes. Like dominant forms, autosomal-recessive forms are generally subdivided into demyelinating forms (autosomal-recessive CMT1: ARCMT1 or CMT4) and axonal forms (ARCMT2). Until now, demyelinating ARCMT were more extensively studied at the genetic level than the axonal forms. Although the latter are undoubtedly the rarest forms among the heterogeneous group of CMT, three distinct forms have been genetically mapped and recent studies in the past 4 yr provided evidence that their respective causing genes have been characterized. Indeed, gene defects in encoding A-type lamins (LMNA), encoding Ganglioside-induced Differentiation-Associated Protein-1 (GDAP1) and encoding the mediator of RNA polymerase II transcription, subunit 25 homolog (MED25) have been identified in ARCMT2 subtypes. Given the clinical, electrophysiological and histological heterogeneity of CMT2, it is likely that unreported forms of ARCMT2, related to novel genes, remain to be discovered, leading to an even more complex classification. However, our goal in this review is to provide the reader with a clear view on the known genes and mechanisms involved in ARCMT2 and their associated phenotypes.
authors.affiliation: Departement de Genetique Medicale Hopital d'enfants de la Timone, Marseille, France.
authors.forename: Rafaëlle
authors.initials: R
authors.lastname: Bernard
authors.forename: Annachiara
authors.initials: A
authors.lastname: De Sandre-Giovannoli
authors.forename: Valérie
authors.initials: V
authors.lastname: Delague
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lévy
mesh_terms: D000818:Animals; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D025063:Chromosome Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002888:Chromosomes, Human, Pair 19; D004195:Disease Models, Animal; D004594:Electrophysiology; D005808:Genes, Recessive / Q000235:genetics*; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism; D008967:Molecular Biology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype
chemical_list: C118663:GDAP protein; C494847:LMNA protein, human; D034904:Lamin Type A; D009419:Nerve Tissue Proteins