title: Congenital hypomyelinating neuropathy due to the association of a truncating mutation in PMP22 with the classical HNPP deletion.
abstract: Congenital hypomyelinating neuropathy appears early in life, resulting in a delay of motor and sensory development. Mutations involve genes such as myelin protein zero (MPZ), peripheral myelin protein 22 (PMP22), and early growth response 2 (EGR2). We present a patient with two compound mutations in PMP22: a point mutation causing a premature STOP codon in exon 3 was inherited from the mother on the first allele, and the "typical" PMP22 deletion in the 17p11.2-p12 region was inherited from the father on the other allele. A sural biopsy was performed at age four. The patient has been followed from 28 months to 21 years of age; he presented significant sensory disturbances, with a slight motor deficit. PMP22 mRNA quantitation showed a severe decrease of PMP22 protein. No myelin sheaths were observed in the biopsy; mesaxons failed to form. The absence of PMP22 provides new insights into the role of this protein.
authors.affiliation: Department 6309, Maintenance Myélinique et Neuropathies Périphériques, Faculté de Médecine de Limoges, Université de Limoges, Limoges, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Jouaud
authors.affiliation: Department of Neurology and Sleep Disorders, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon, France.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Gonnaud
authors.affiliation: Department of Neurology, National Reference Center for Rare Peripheral Neuropathies, University Hospital, Limoges, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Richard
authors.affiliation: Department of Biochemistry, Centre de Biologie Est, Hospices Civils de Lyon, Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Latour
authors.affiliation: Department of Genetics, Hospices Civils de Lyon, Lyon, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ollagnon-Roman
authors.affiliation: Department 6309, Maintenance Myélinique et Neuropathies Périphériques, Faculté de Médecine de Limoges, Université de Limoges, Limoges, France; Department of Biochemistry and Genetics, CHU de Limoges, Equipe d'accueil 6309, Maintenance Myélinique et Neuropathies Périphériques, Université de Limoges, Limoges, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Sturtz
authors.affiliation: Department of Neurology, CHU Poitiers, University of Poitiers, 2 Rue de la Milétrie, 86021 Poitiers, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mathis
authors.affiliation: Department of Neurology, National Reference Center for Rare Peripheral Neuropathies, University Hospital, Limoges, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Magy
authors.affiliation: Department of Neurology, National Reference Center for Rare Peripheral Neuropathies, University Hospital, Limoges, France. Electronic address: jean-michel.vallat@unilim.fr.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Vallat
mesh_terms: D001706:Biopsy; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002675:Child, Preschool; D006801:Humans; D008297:Male; D009185:Myelin Proteins / Q000235:genetics* / Q000378:metabolism; D009431:Neural Conduction / Q000235:genetics; D017354:Point Mutation; D012333:RNA, Messenger / Q000378:metabolism; D017384:Sequence Deletion; D013497:Sural Nerve / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult
chemical_list: D009185:Myelin Proteins; C073687:PMP22 protein, human; D012333:RNA, Messenger
keywords: CMT; Congenital hypomyelinating neuropathy; Nerve biopsy; PMP22