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New insights into the pathological mechanisms of cerebrotendinous xanthomatosis in the Taiwanese using genomic and proteomic tools
Author(s) -
Wang PeiWeg,
Chang WenNeng,
Lu ChenHsin,
Chao David,
Schrag Christiaan,
Pan TaiLong
Publication year - 2006
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200500159
Subject(s) - cerebrotendinous xanthomatosis , frameshift mutation , biology , genomic dna , blot , proteomics , exon , point mutation , microbiology and biotechnology , genetics , dna , mutation , gene , biochemistry , cholesterol
Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid‐storage disorder caused by a deficiency of the mitochondrial sterol 27‐hydroxylase. Genetic analysis utilizing SSCP and direct DNA sequencing identified a new mutation. One base‐pair of cytosine was deleted at codon 326 on exon 2 of CYP27 in all CTX patients while their father was heterozygotic. This novel point deletion predicts a frameshift in mRNA (Pro 102 →Leu) and results in the appearance of a premature termination codon (TGA) to substitute for Val 106 (GTG). To characterize the pathological mechanism of CTX patients, the protein profiles of serum and leukocytes extracted from these subjects were presented by means of proteomic technologies including 2‐DE and MALDI‐TOF analysis. According to the results, the amount of vinculin, ABP‐280, talin and vimentin in leukocytes of CTX patients had changed significantly, reflecting the changes in membrane dynamics concerning cholestanol accumulation. The expression of target proteins in CTX patients and control was further verified by western blotting which indicated the same tendency as 2‐DE data. This is the first paper to integrate both genomic and proteomic concepts for analyzing the possible mechanism of CTX and provides more information for related study in the future.