BACKGROUND: A biomarker for the diagnosis of childhood-onset ataxia and central nervous system hypomyelination (CACH)/vanishing white matter disease (VWM) would have clinical utility and pathophysiologic significance. METHODS: We used 2-dimensional gel electrophoresis/mass spectrometry to compare the cerebrospinal fluid proteome of patients with mutation-confirmed CACH/VWM with that of unaffected controls. We characterized selected spots by in-gel digestion, matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry, and nanospray Fourier transform mass spectrometry. RESULTS: A specific transferrin spot pattern was detected in the CSF samples of the CACH/VWM group (n = 7), distinguishing them from the control group (n = 23) and revealing that patients with CACH/VWM have a deficiency of the asialo form of transferrin usually present in healthy cerebrospinal fluid. The glycopeptide structure, determined from isolated transferrin spots by use of in-gel digestion and extraction, was found to be consistent with earlier reports. CONCLUSIONS: The transferrin isoform abnormality in the cerebrospinal fluid of patients with CACH/VWM appears unique and is a potential clinical diagnostic biomarker. The rapid, efficient diagnosis of this disorder would have a significant impact on clinical studies exploring new strategies for the management and treatment of this disease.
BACKGROUND: A biomarker for the diagnosis of childhood-onset ataxia and central nervous system hypomyelination (CACH)/vanishing white matter disease (VWM) would have clinical utility and pathophysiologic significance. METHODS: We used 2-dimensional gel electrophoresis/mass spectrometry to compare the cerebrospinal fluid proteome of patients with mutation-confirmed CACH/VWM with that of unaffected controls. We characterized selected spots by in-gel digestion, matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry, and nanospray Fourier transform mass spectrometry. RESULTS: A specific transferrin spot pattern was detected in the CSF samples of the CACH/VWM group (n = 7), distinguishing them from the control group (n = 23) and revealing that patients with CACH/VWM have a deficiency of the asialo form of transferrin usually present in healthy cerebrospinal fluid. The glycopeptide structure, determined from isolated transferrin spots by use of in-gel digestion and extraction, was found to be consistent with earlier reports. CONCLUSIONS: The transferrin isoform abnormality in the cerebrospinal fluid of patients with CACH/VWM appears unique and is a potential clinical diagnostic biomarker. The rapid, efficient diagnosis of this disorder would have a significant impact on clinical studies exploring new strategies for the management and treatment of this disease.
Authors: Meena U Rajagopal; Yetrib Hathout; Tobey J MacDonald; Mark W Kieran; Sri Gururangan; Susan M Blaney; Peter Phillips; Roger Packer; Heather Gordish-Dressman; Brian R Rood Journal: Proteomics Date: 2011-01-27 Impact factor: 3.984
Authors: David E Connor; Ganta V Chaitanya; Prashant Chittiboina; Paul McCarthy; L Keith Scott; Lisa Schrott; Alireza Minagar; Anil Nanda; J Steven Alexander Journal: Pathophysiology Date: 2017-05-13
Authors: A Vanderver; Y Hathout; J Maletkovic; E S Gordon; M Mintz; M Timmons; E P Hoffman; L Horzinski; F Niel; A Fogli; O Boespflug-Tanguy; R Schiffmann Journal: Neurology Date: 2008-06-03 Impact factor: 9.910
Authors: F Mochel; F Sedel; A Vanderver; U F H Engelke; J Barritault; B Z Yang; B Kulkarni; D R Adams; F Clot; J H Ding; C R Kaneski; F W Verheijen; B W Smits; F Seguin; A Brice; M T Vanier; M Huizing; R Schiffmann; A Durr; R A Wevers Journal: Brain Date: 2009-01-19 Impact factor: 13.501