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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Acknowledgements
We thank Dr R Brackmann (Herford) and Dr P Navratil (Coesfeld) for referring patients for further investigations. In addition, the technical assistance of Ingrid DuChesne and Ilka Neumann is acknowledged.
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Häberle, J., Pauli, S., Berning, C. et al. TC II deficiency: avoidance of false-negative molecular genetics by RNA-based investigations. J Hum Genet 54, 331–334 (2009). https://doi.org/10.1038/jhg.2009.34
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DOI: https://doi.org/10.1038/jhg.2009.34
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