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TC II deficiency: avoidance of false-negative molecular genetics by RNA-based investigations


Häberle, J; Pauli, S; Berning, C; Koch, H G; Linnebank, M (2009). TC II deficiency: avoidance of false-negative molecular genetics by RNA-based investigations. Journal of Human Genetics, 54(6):331-334.

Abstract

Transcobalamin II (TC II) is a plasma transport protein for cobalamin. TC II deficiency can lead to infant megaloblastic anemia, failure to thrive and to neurological complications. This report describes the genetic work-up of three patients who presented in early infancy. Initially, genomic investigations did not reveal the definite genetic diagnosis in the two index patients. However, analysis of cDNA from skin fibroblasts revealed a homozygous deletion of exon 7 of the TC II gene caused by the mutation c.940+303_c.1106+746del2152insCTGG (r.941_1105del; p.fs326X) in one patient. The other patients were siblings and both affected by an insertion of 87 bp on the transcript which was caused by the homozygous mutation c.580+624A>T (r.580ins87; p.fs209X). Additional experiments showed that cDNA from lymphocytes could have been used also for the genetic work-up. This report shows that the use of cDNA from skin fibroblasts or peripheral lymphocytes facilitates genetic investigations of suspected TC II deficiency and helps to avoid false-negative DNA analysis.

Abstract

Transcobalamin II (TC II) is a plasma transport protein for cobalamin. TC II deficiency can lead to infant megaloblastic anemia, failure to thrive and to neurological complications. This report describes the genetic work-up of three patients who presented in early infancy. Initially, genomic investigations did not reveal the definite genetic diagnosis in the two index patients. However, analysis of cDNA from skin fibroblasts revealed a homozygous deletion of exon 7 of the TC II gene caused by the mutation c.940+303_c.1106+746del2152insCTGG (r.941_1105del; p.fs326X) in one patient. The other patients were siblings and both affected by an insertion of 87 bp on the transcript which was caused by the homozygous mutation c.580+624A>T (r.580ins87; p.fs209X). Additional experiments showed that cDNA from lymphocytes could have been used also for the genetic work-up. This report shows that the use of cDNA from skin fibroblasts or peripheral lymphocytes facilitates genetic investigations of suspected TC II deficiency and helps to avoid false-negative DNA analysis.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2009
Deposited On:02 Nov 2009 13:54
Last Modified:05 Apr 2016 13:31
Publisher:Springer
ISSN:1434-5161
Additional Information:The original publication is available at www.springerlink.com
Publisher DOI:https://doi.org/10.1038/jhg.2009.34
PubMed ID:19373259

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