Telomere length measurement can distinguish pathogenic from non-pathogenic variants in the shelterin component, TIN2
Article first published online: 4 JAN 2011
© 2011 John Wiley & Sons A/S
Volume 81, Issue 1, pages 76–81, January 2012
How to Cite
Vulliamy, T., Beswick, R., Kirwan, M., Hossain, U., Walne, A. and Dokal, I. (2012), Telomere length measurement can distinguish pathogenic from non-pathogenic variants in the shelterin component, TIN2. Clinical Genetics, 81: 76–81. doi: 10.1111/j.1399-0004.2010.01605.x
- Issue published online: 12 DEC 2011
- Article first published online: 4 JAN 2011
- Accepted manuscript online: 6 DEC 2010 08:10AM EST
- Received 1 October 2010, revised and accepted for publication 30 November 2010
- bone marrow failure;
- dyskeratosis congenita;
- telomere length
Vulliamy T, Beswick R, Kirwan MJ, Hossain U, Walne AJ, Dokal I. Telomere length measurement can distinguish pathogenic from non-pathogenic variants in the shelterin component, TIN2.
Dyskeratosis congenita (DC) is a heterogeneous bone marrow failure syndrome with seven disease-causing genes identified to date, six of which are linked to telomere maintenance. Mutations in one of these genes (TINF2), which encodes a component of the shelterin complex, are associated with particularly short telomeres. Among the 224 consecutive patients with different forms of bone marrow failure (46 with DC, 122 with aplastic anaemia and 57 with some features of DC), we have identified 16 new families with variants in exon 6 of the TINF2 gene, eight of which are novel. We observe that the phenotype associated with these mutations extends to a severe early presentation, not always classified as DC. In addition, we see that some of the variants identified are not associated with short telomeres and are also found in asymptomatic individuals. In the absence of any direct functional assay, the data indicates that the telomere length measurement can inform us as to which variants in TINF2 are pathogenic and which may be non-pathogenic.