title: Duplication of the PMP22 gene in 17p partial trisomy patients with Charcot-Marie-Tooth type-1 neuropathy.
abstract: Autosomal dominant Charcot-Marie-Tooth type-1A neuropathy (CMT1A) is a demyelinating peripheral nerve disorder that is commonly associated with a submicroscopic tandem DNA duplication of a 1.5-Mb region of 17p11.2p12 that contains the peripheral myelin gene PMP22. Clinical features of CMT1A include progressive distal muscle atrophy and weakness, foot and hand deformities, gait abnormalities, absent reflexes, and the completely penetrant electrophysiologic phenotype of symmetric reductions in motor nerve conduction velocities (NCVs). Molecular and fluorescense in situ hybridization (FISH) analyses were performed to determine the duplication status of the PMP22 gene in four patients with rare cytogenetic duplications of 17p. Neuropathologic features of CMT1A were seen in two of these four patients, in addition to the complex phenotype asociated with 17p partial trisomy. Our findings show that the CMT1A phenotype of reduced NCV is specifically associated with PMP22 gene duplications, thus providing further support for the PMP22 gene dosage mechanism for CMT1A.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: B B
authors.initials: BB
authors.lastname: Roa
authors.forename: F
authors.initials: F
authors.lastname: Greenberg
authors.forename: P
authors.initials: P
authors.lastname: Gunaratne
authors.forename: C M
authors.initials: CM
authors.lastname: Sauer
authors.forename: M S
authors.initials: MS
authors.lastname: Lubinsky
authors.forename: C
authors.initials: C
authors.lastname: Kozma
authors.forename: J M
authors.initials: JM
authors.lastname: Meck
authors.forename: R E
authors.initials: RE
authors.lastname: Magenis
authors.forename: L G
authors.initials: LG
authors.lastname: Shaffer
authors.forename: J R
authors.initials: JR
authors.lastname: Lupski
mesh_terms: D015139:Blotting, Southern; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002675:Child, Preschool; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D004594:Electrophysiology; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009046:Motor Neurons / Q000502:physiology; D005810:Multigene Family; D009185:Myelin Proteins / Q000235:genetics*; D009431:Neural Conduction; D010375:Pedigree; D010641:Phenotype; D013497:Sural Nerve / Q000503:physiopathology; D014314:Trisomy
chemical_list: D009185:Myelin Proteins; C073687:PMP22 protein, human