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False low holotranscobalamin levels in a patient with a novel TCN2 mutation

Keller, Peter ; Rufener, Janine ; Schild, Christof ; Fedosov, Sergey N. ; Nissen, Peter H. ; Nexo, Ebba

In: Clinical Chemistry and Laboratory Medicine (CCLM), 2016, vol. 54, no. 11, p. 1739-1743

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    Titre
    • False low holotranscobalamin levels in a patient with a novel TCN2 mutation
    Auteur
    • Keller, Peter. Central Hematology Laboratory, University Clinic of Hematology, Bern University Hospital, Inselspital, Freiburgstr, Bern 3010, Switzerland, Phone: +41316321390, Fax: +41316323406
    • Rufener, Janine. Central Hematology Laboratory, University Clinic of Hematology, Bern University Hospital, Inselspital, Bern, Switzerland
    • Schild, Christof. University Institute of Clinical Chemistry, Bern University Hospital, Inselspital, Bern, Switzerland
    • Fedosov, Sergey N.. Department of Molecular Biology and Genetics, Molecular Nutrition, Aarhus University, Aarhus, Denmark
    • Nissen, Peter H.. Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
    • Nexo, Ebba. Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Clinical Chemistry and Laboratory Medicine (CCLM), 2016, vol. 54, no. 11, p. 1739-1743. De Gruyter
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:326208
    Summary
    AbstractBackground: Measurement of holotranscobalamin (holoTC) is increasingly used as a screening test for cobalamin (Cbl) deficiency. A level well below the reference interval strongly supports a deficient state. We examined a 21-year-old woman diagnosed as Cbl deficient because of an extremely low holoTC level as measured by the Abbott Architect Assay. Methods: The patient was evaluated for Cbl deficiency employing an in-house holoTC method as well as other routine markers of Cbl status. Further analyses included exploration of the Cbl binding proteins employing gel filtration of a serum sample saturated with 57 Co-labeled Cbl and Sanger sequencing of exons 1-9 and the intron-exon boundaries of the TCN2 gene, the gene coding for transcobalamin (TC). Results: The patient had normal hematological variables throughout. Despite initial treatment with Cbl, holoTC as measured by the Abbott assay remained low, while holoTC measured with the in-house assay was normal, and behaved as TC upon gel-filtration. By Sanger sequencing, we detected a homozygous single point mutation c.855T>A in exon 6 of TCN2, corresponding to a asparagine (Asn) to lysine (Lys) substitution in position 267 of the mature protein. Conclusions: We describe a novel point mutation of the TCN2 gene. The mutation does not seem to interfere with the function of TC, but the mutation may well explain the low level of holoTC detected by the Abbott assay. Our results underscores that mutations of TCN2 have to be considered when implausible holoTC results are obtained.