Andrea Zühlsdorf1, Julien Heinrich Park1, Yoshinao Wada2, Stephan Rust1, Janine Reunert1, Ingrid DuChesne1, Marianne Grüneberg1, Thorsten Marquardt3. 1. Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin - Allgemeine Pädiatrie, Albert Schweitzer Campus 1, Gebäude A 1, 48149 Münster, Germany. 2. Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka University, 840 Murodo-cho, Izumi, Osaka 594-1101, Japan. 3. Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin - Allgemeine Pädiatrie, Albert Schweitzer Campus 1, Gebäude A 1, 48149 Münster, Germany. Electronic address: marquat@uni-muenster.de.
Abstract
OBJECTIVES: Transferrin variants can hinder the diagnostic process in cases of suspected Congenital disorders of glycosylation which affect N-Glycosylation. In addition they can impair the use of Carbohydrate deficient Transferrin as a biomarker for chronic alcohol abuse, in which Asialo-Transferrin and Disialo-Transferrin are increased. We present a novel transferrin variant as well as an overview of transferrin mutations found at our laboratory. DESIGN AND METHODS: Blood samples from patients with suspected CDG were analyzed using the standard diagnostic procedures of Isoelectric focusing and High-performance liquid chromatography as well as the additional procedures of neuraminidase digestion of glycans and Electrospray ionization time-of-flight mass spectrometry (ESI-TOF MS). RESULTS: Four known and one previously unreported transferrin variants were identified. Neuraminidase digestion and ESI-TOF MS revealed changes in charge of the transferrin molecules while the glycosylation status was found to be normal. CONCLUSION: Transferrin variants are pitfalls in the diagnostics of CDG. The found variants change the charge of the transferrin molecule, thus affecting the standard diagnostic procedures. Neuraminidase digestion as well as ESI-TOF MS can identify variants and mutations in a laboratory context.
OBJECTIVES:Transferrin variants can hinder the diagnostic process in cases of suspected Congenital disorders of glycosylation which affect N-Glycosylation. In addition they can impair the use of Carbohydrate deficient Transferrin as a biomarker for chronic alcohol abuse, in which Asialo-Transferrin and Disialo-Transferrin are increased. We present a novel transferrin variant as well as an overview of transferrin mutations found at our laboratory. DESIGN AND METHODS: Blood samples from patients with suspected CDG were analyzed using the standard diagnostic procedures of Isoelectric focusing and High-performance liquid chromatography as well as the additional procedures of neuraminidase digestion of glycans and Electrospray ionization time-of-flight mass spectrometry (ESI-TOF MS). RESULTS: Four known and one previously unreported transferrin variants were identified. Neuraminidase digestion and ESI-TOF MS revealed changes in charge of the transferrin molecules while the glycosylation status was found to be normal. CONCLUSION:Transferrin variants are pitfalls in the diagnostics of CDG. The found variants change the charge of the transferrin molecule, thus affecting the standard diagnostic procedures. Neuraminidase digestion as well as ESI-TOF MS can identify variants and mutations in a laboratory context.
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