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Genomic mutations associated with mild and severe deficiencies of transcobalamin I (haptocorrin) that cause mildly and severely low serum cobalamin levels.
Br J Haematol. 2009 Nov; 147(3):386-91.BJ

Abstract

Transcobalamin (TC) I deficiency, like the function of TC I itself, is incompletely understood. It produces low serum cobalamin levels indistinguishable from those of true cobalamin deficiency. Diagnosis is especially elusive when TC I deficiency is mild. To provide new, more substantive definition, the TCN1 gene was examined in two well-characterised families that included members with both severe and mild TC I deficiencies. A severely deficient proposita with undetectable TC I levels displayed compound heterozygosity for two mutations, each causing a premature stop codon. Relatives in both families who had mildly low or low-normal plasma levels of TC I and cobalamin were heterozygous for one or the other of these mutations. An unrelated patient with mild TC I deficiency and unknown familial TC I and cobalamin status was then tested and found to be similarly heterozygous for one of the mutations. The two nonprivate mutations identify a genetic basis for TC I deficiency for the first time. They also add new approaches to studying mild and severe TC I deficiency and to reducing confusion of its low cobalamin levels with those of cobalamin deficiency and its often dramatically different prognosis and management.

Authors+Show Affiliations

Department of Medicine, New York Methodist Hospital, Brooklyn, NY 11215, USA. rac9001@nyp.orgNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19686235

Citation

Carmel, Ralph, et al. "Genomic Mutations Associated With Mild and Severe Deficiencies of Transcobalamin I (haptocorrin) That Cause Mildly and Severely Low Serum Cobalamin Levels." British Journal of Haematology, vol. 147, no. 3, 2009, pp. 386-91.
Carmel R, Parker J, Kelman Z. Genomic mutations associated with mild and severe deficiencies of transcobalamin I (haptocorrin) that cause mildly and severely low serum cobalamin levels. Br J Haematol. 2009;147(3):386-91.
Carmel, R., Parker, J., & Kelman, Z. (2009). Genomic mutations associated with mild and severe deficiencies of transcobalamin I (haptocorrin) that cause mildly and severely low serum cobalamin levels. British Journal of Haematology, 147(3), 386-91. https://doi.org/10.1111/j.1365-2141.2009.07855.x
Carmel R, Parker J, Kelman Z. Genomic Mutations Associated With Mild and Severe Deficiencies of Transcobalamin I (haptocorrin) That Cause Mildly and Severely Low Serum Cobalamin Levels. Br J Haematol. 2009;147(3):386-91. PubMed PMID: 19686235.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genomic mutations associated with mild and severe deficiencies of transcobalamin I (haptocorrin) that cause mildly and severely low serum cobalamin levels. AU - Carmel,Ralph, AU - Parker,James, AU - Kelman,Zvi, Y1 - 2009/08/17/ PY - 2009/8/19/entrez PY - 2009/8/19/pubmed PY - 2010/2/24/medline SP - 386 EP - 91 JF - British journal of haematology JO - Br J Haematol VL - 147 IS - 3 N2 - Transcobalamin (TC) I deficiency, like the function of TC I itself, is incompletely understood. It produces low serum cobalamin levels indistinguishable from those of true cobalamin deficiency. Diagnosis is especially elusive when TC I deficiency is mild. To provide new, more substantive definition, the TCN1 gene was examined in two well-characterised families that included members with both severe and mild TC I deficiencies. A severely deficient proposita with undetectable TC I levels displayed compound heterozygosity for two mutations, each causing a premature stop codon. Relatives in both families who had mildly low or low-normal plasma levels of TC I and cobalamin were heterozygous for one or the other of these mutations. An unrelated patient with mild TC I deficiency and unknown familial TC I and cobalamin status was then tested and found to be similarly heterozygous for one of the mutations. The two nonprivate mutations identify a genetic basis for TC I deficiency for the first time. They also add new approaches to studying mild and severe TC I deficiency and to reducing confusion of its low cobalamin levels with those of cobalamin deficiency and its often dramatically different prognosis and management. SN - 1365-2141 UR - https://www.unboundmedicine.com/medline/citation/19686235/Genomic_mutations_associated_with_mild_and_severe_deficiencies_of_transcobalamin_I__haptocorrin__that_cause_mildly_and_severely_low_serum_cobalamin_levels_ L2 - https://doi.org/10.1111/j.1365-2141.2009.07855.x DB - PRIME DP - Unbound Medicine ER -