title: Diagnostic value of ultrastructural nerve examination in Charcot-Marie-Tooth disease: two CMT 1B cases with pseudo-recessive inheritance.
abstract: We report two sporadic patients of CMT disease in different consanguineous families. The electrophysiological examination led to the diagnosis of a severe demyelinating neuropathy. The nerve biopsies exhibited numerous outfoldings of the myelin sheaths and onion-bulb proliferations. The consanguinity and the histological findings pointed to a diagnosis of CMT 4B. However, the detection of abnormal and regular widenings between the major dense lines of the myelin lamellae by electron microscopy led us to search for a P0 gene mutation. Two heterozygous mutations of this gene were identified: S63F and N131Y. Different aspects of uncompacted myelin lamellae have been described in some cases of P0 mutations and a few now appear to be quite specific to it. More than 30 genes are implicated in CMT and as mutation search is time- and money-consuming, we believe that in some selected patients ultrastructural examination of nerves, among other criteria, helps orientate the molecular diagnosis of CMT.
authors.affiliation: Department of Neurology et Centre National de Référence des Neuropathies Périphériques Rares, University Hospital, 2 Avenue Martin Luther King, 87042, Limoges Cedex, France. jean-michel.vallat@unilim.fr
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Vallat
authors.forename: Laurent
authors.initials: L
authors.lastname: Magy
authors.forename: Emmeline
authors.initials: E
authors.lastname: Lagrange
authors.forename: Franck
authors.initials: F
authors.lastname: Sturtz
authors.forename: Corinne
authors.initials: C
authors.lastname: Magdelaine
authors.forename: Djamel
authors.initials: D
authors.lastname: Grid
authors.forename: Mériem
authors.initials: M
authors.lastname: Tazir
mesh_terms: D000328:Adult; D001216:Asparagine / Q000235:genetics; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis* / Q000235:genetics*; D002648:Child; D003241:Consanguinity; D004252:DNA Mutational Analysis / Q000379:methods; D003711:Demyelinating Diseases / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D018993:Myelin P0 Protein / Q000235:genetics*; D009186:Myelin Sheath / Q000648:ultrastructure; D010525:Peripheral Nerves / Q000473:pathology / Q000648:ultrastructure; D010649:Phenylalanine / Q000235:genetics; D012694:Serine / Q000235:genetics; D014443:Tyrosine / Q000235:genetics
chemical_list: D018993:Myelin P0 Protein; D014443:Tyrosine; D012694:Serine; D010649:Phenylalanine; D001216:Asparagine