The peripheral myelin gene PMP-22/GAS-3 is duplicated in Charcot-Marie-Tooth disease type 1A.
Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with a DNA duplication at chromosome 17p11.2. In view of the point mutation in the gene for peripheral myelin protein pmp-22/gas-3 in Trembler mice, a murine model for CMT1A, we have analysed whether this gene is altered in CMT1A. Here we show that the human homologue of the murine pmp-22 gene is located within the CMT1A DNA duplication, which is a direct repeat and does not interrupt the coding region of PMP-22. Expression of PMP-22 in CMT1A fibroblasts is similar to expression in control fibroblasts. Increased gene dosage or altered PMP-22 expression in the peripheral nervous system are therefore possible mechanisms by which PMP-22 is involved in CMT1A.
Valentijn
L J
LJ
Department of Neurology, Academical Medical Center, Amsterdam, The Netherlands.
Bolhuis
P A
PA
Zorn
I
I
Hoogendijk
J E
JE
van den Bosch
N
N
Hensels
G W
GW
Stanton
V P
VP
Housman
D E
DE
Fischbeck
K H
KH
Ross
D A
DA
D001483:Base Sequence; D002607:Charcot-Marie-Tooth Disease / Q000145:classification / Q000235:genetics*; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D009185:Myelin Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid
D009185:Myelin Proteins; C073687:PMP22 protein, human; D004247:DNA