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 (2016). False low holotranscobalamin levels in a patient with a novel TCN2 mutation. Clinical chemistry and laboratory medicine, 54(11), pp. 1739-1743. De Gruyter 10.1515/cclm-2016-0063

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BACKGROUND 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.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)

UniBE Contributor:

Keller, Peter; Rufener, Janine and Schild, Christof

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1434-6621

Publisher:

De Gruyter

Language:

English

Submitter:

Verena Zwahlen

Date Deposited:

20 Feb 2017 15:29

Last Modified:

22 Sep 2017 11:05

Publisher DOI:

10.1515/cclm-2016-0063

PubMed ID:

27155006

BORIS DOI:

10.7892/boris.83964

URI:

https://boris.unibe.ch/id/eprint/83964

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