Gene dosage sensitivity of a novel mutation in the intracellular domain of P0 associated with Charcot-Marie-Tooth disease type 1B.
Autosomal dominant Charcot-Marie-Tooth disease type 1B (CMT1B) is caused by heterozygous mutations in the extracellular domain of P0. Here, we investigated clinically, electrophysiologically and pathologically a pedigree with a novel mutation in the intracellular domain of P0 (P0ic). The mutational analysis included denaturing high performance liquid chromatography (DHPLC) and nucleotide sequencing. Two patients from subsequent generations were homozygous for an Asp195Tyr mutation in the intracellular domain of P0 (P0ic), whereas two healthy individuals with minimal electrophysiological changes were heterozygous for the same mutation. The authors conclude that mutations of P0ic may undergo a gene dosage effect manifesting semidominant inheritance.
Section of Clinical Neurology, Department of Neurological and Visual Sciences, University of Verona, Policlinico G.B. Rossi, P.le L.A. Scuro 10, 37134 Verona, Italy. gianmaria.fabrizi@univr.it
Gian Maria
GM
Fabrizi
Maria
M
Pellegrini
Chiara
C
Angiari
Tiziana
T
Cavallaro
Alberto
A
Morini
Federica
F
Taioli
Ilaria
I
Cabrini
Daniele
D
Orrico
Nicolò
N
Rizzuto
D000328:Adult; D000368:Aged; D001224:Aspartic Acid / Q000235:genetics; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons; D005192:Family Health; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008969:Molecular Sequence Data; D009154:Mutation; D018993:Myelin P0 Protein / Q000235:genetics*; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000648:ultrastructure; D010375:Pedigree; D017434:Protein Structure, Tertiary / Q000235:genetics; D014443:Tyrosine / Q000235:genetics
D018993:Myelin P0 Protein; D001224:Aspartic Acid; D014443:Tyrosine