Skin biopsies in myelin-related neuropathies: bringing molecular pathology to the bedside.
Skin biopsy is a minimally invasive procedure and has been used in the evaluation of non-myelinated, but not myelinated nerve fibres, in sensory neuropathies. We therefore evaluated myelinated nerves in skin biopsies from normal controls and patients with Charcot-Marie-Tooth (CMT) disease caused by mutations in myelin proteins. Light microscopy, electron microscopy and immunohistochemistry routinely identified myelinated dermal nerves in glabrous skin that appeared similar to myelinated fibres in sural and sciatic nerve. Myelin abnormalities were observed in all patients with CMT. Moreover, skin biopsies detected potential pathogenic abnormalities in the axolemmal molecular architecture previously undetected in human neuropathies. Finally, myelin gene expression at both mRNA and protein levels was evaluated by real-time PCR and immunoelectron microscopy. Peripheral myelin protein 22 (PMP22) was increased in CMT1A (PMP22 duplication) and decreased in patients with hereditary neuropathy with liability to pressure palsies (PMP22 deletion). Taken together, our data suggest that skin biopsy may in certain circumstances replace the more invasive sural nerve biopsy in the morphological and molecular evaluation of inherited and other demyelinating neuropathies.
Li
Jun
J
Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201, USA. junli@med.wayne.edu
Bai
Yunhong
Y
Ghandour
Khaled
K
Qin
Pu
P
Grandis
Marina
M
Trostinskaia
Anna
A
Ianakova
Emilia
E
Wu
Xingyao
X
Schenone
Angelo
A
Vallat
Jean-Michel
JM
Kupsky
William J
WJ
Hatfield
James
J
Shy
Michael E
ME
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D009185:Myelin Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000648:ultrastructure*; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000294:innervation* / Q000648:ultrastructure*
D009185:Myelin Proteins; C073687:PMP22 protein, human; D012333:RNA, Messenger