Underexpression of messenger RNA for peripheral myelin protein 22 in hereditary neuropathy with liability to pressure palsies.
Hereditary neuropathy with liability to pressure palsies (HNPP) is associated with a deletion in chromosome 17p11.2, including the gene for the peripheral myelin protein 22 (PMP-22). Because of the proposal that a decreased dosage of the PMP-22 gene was the cause of HNPP, we evaluated sural nerves from eight patients with the 17p11.2 deletion and from five normal controls. The relative amount of PMP-22 mRNA was significantly lower in HNPP patients compared with normal controls (p < 0.02) using a semiquantitative reverse transcriptase-polymerase chain reaction. There was no significant decrease of Pzero mRNA. Sural nerves from HNPP patients showed normal immunostaining with monoclonal antibodies against PMP-22, Pzero, and myelin basic protein, and only rare myelinated fibers, classified as "tomacula," showed a patchy staining of the compact myelin with monoclonal antibody against PMP-22. The significant underexpression of PMP-22 mRNA in HNPP patients compared with normal controls demonstrates that a decreased dosage of the PMP-22 gene is the most likely pathogenetic mechanism in HNPP.
Schenone
A
A
Department of Neurological Sciences, University of Genoa, Italy.
Nobbio
L
L
Mandich
P
P
Bellone
E
E
Abbruzzese
M
M
Aymar
F
F
Mancardi
G L
GL
Windebank
A J
AJ
D001483:Base Sequence; D004487:Edema / Q000473:pathology; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000235:genetics*; D009186:Myelin Sheath; D010243:Paralysis / Q000235:genetics* / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000473:pathology; D011312:Pressure; D012333:RNA, Messenger / Q000235:genetics*; D012008:Recurrence
D009185:Myelin Proteins; C073687:PMP22 protein, human; D012333:RNA, Messenger