Abstract:
OBJECTIVES:In the process of obtaining a driver's license, a healthy 28year old man presented increased levels of disialo-transferrin (TF) (approx. 20%, ref. value<2) by HPLC analysis of TF isoforms (%CDT), while other markers of excessive alcohol consumption (PEth, MCV and γ-GT) were in the normal range. The objective of this study was to determine the cause of the increased %CDT levels. DESIGN AND METHODS:Serum TF isoforms were re-analyzed by LC-MS. All coding exons of the TF gene were Sanger sequenced. RESULTS:Analysis of TF isoforms by LC-MS confirmed the presence of increased disialo-TF and revealed a discrepancy in the mass difference between disialo-TF and tetrasialo-TF which suggested the presence of a genetic TF isoform with one abolished N-glycosylation site. Sanger sequencing of the TF gene revealed the presence of two missense mutations in heterozygous form: c.1295A>G (p.N432S) and c.1765C>T (p.P589S). p.N432S is a novel mutation that abolishes one N-glycosylation site of TF, while p.P589S is the polymorphism that defines the C2 isoform of TF. The sum of mass shifts caused by both amino acid substitutions agrees with the mass shift observed by LC-MS, which indicates that both variants are located in cis. CONCLUSIONS:An individual initially suspected of alcohol abuse based on elevated %CDT was shown to be carrier of a novel mutation in the TF gene that abolishes the N-glycosylation site at position p.N432. The presence of this genetic variant has to be kept in mind when interpreting TF isoform patterns.
journal_name
Clin Biochemjournal_title
Clinical biochemistryauthors
Grahn A,Bengtson P,Eklund E,Asin-Cayuela Jdoi
10.1016/j.clinbiochem.2015.12.001subject
Has Abstractpub_date
2016-04-01 00:00:00pages
511-513issue
6eissn
0009-9120issn
1873-2933pii
S0009-9120(15)00556-1journal_volume
49pub_type
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更新日期:2002-11-01 00:00:00
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更新日期:2011-08-01 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2014-09-01 00:00:00
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更新日期:1978-12-01 00:00:00
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更新日期:2006-01-01 00:00:00
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更新日期:2000-08-01 00:00:00
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更新日期:1998-06-01 00:00:00
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更新日期:2017-04-01 00:00:00
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更新日期:2006-03-01 00:00:00