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Eur J Hum Genet. 2018 Jun;26(6):858-867. doi: 10.1038/s41431-018-0112-8. Epub 2018 Feb 26.

Novel variants in Nordic patients referred for genetic testing of telomere-related disorders.

Author information

1
Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, Umeå, Sweden. anna.norberg@vll.se.
2
Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, Umeå, Sweden.
3
Department of Radiation sciences, Oncology, Umeå University, Umeå, Sweden.
4
Department of Hematology X, Odense University Hospital, Odense, Denmark.
5
Department of Hematology, National University Hospital of Copenhagen Rigshospitalet, Copenhagen, Denmark.
6
PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu, Oulu, Finland.
7
Department of Clinical Genetics, Oulu University Hospital, Oulu, Finland.
8
Department of Clinical Genetics, Uppsala University Hospital, Uppsala, Sweden.
9
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
10
Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland.
11
Department of Medicine, Section of Hematology, Haukeland University Hospital, Bergen, Norway.
12
Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.

Abstract

Telomere-related disorders are a clinically and genetically heterogeneous group of disorders characterized by premature telomere shortening and proliferative failure of a variety of tissues. This study reports the spectrum of telomere-related gene variants and telomere length in Nordic patients referred for genetic testing due to suspected telomere-related disorder. We performed Sanger sequencing of the genes TERT, TERC, DKC1, and TINF2 on 135 unrelated index patients and measured telomere length by qPCR on DNA from peripheral blood leukocytes. We identified pathogenic or likely pathogenic variants in 10 index patients, all of which had short telomeres compared to age-matched healthy controls. Six of the 10 variants were novel; three in TERC (n.69_74dupAGGCGC, n.122_125delGCGG, and n.407_408delinsAA) and three in TERT (p.(D684G), p.(R774*), and p.(*1133Wext*39)). The high proportion of novel variants identified in our study highlights the need for solid interpretation of new variants that may be detected. Measurement of telomere length is a useful approach for evaluating pathogenicity of genetic variants associated with telomere-related disorders.

PMID:
29483670
PMCID:
PMC5974393
DOI:
10.1038/s41431-018-0112-8
[Indexed for MEDLINE]
Free PMC Article

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