Diagnostics of rare disorders: whole-exome sequencing deciphering locus heterogeneity in telomere biology disorders

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dc.contributor.author Trotta, Luca
dc.contributor.author Norberg, Anna
dc.contributor.author Taskinen, Mervi
dc.contributor.author Béziat, Vivien
dc.contributor.author Degerman, Sofie
dc.contributor.author Wartiovaara-Kautto, Ulla
dc.contributor.author Välimaa, Hannamari
dc.contributor.author Jahnukainen, Kirsi
dc.contributor.author Casanova, Jean-Laurent
dc.contributor.author Seppänen, Mikko
dc.contributor.author Saarela, Janna
dc.contributor.author Koskenvuo, Minna
dc.contributor.author Martelius, Timi
dc.date.accessioned 2018-08-19T03:24:32Z
dc.date.available 2018-08-19T03:24:32Z
dc.date.issued 2018-08-17
dc.identifier.citation Orphanet Journal of Rare Diseases. 2018 Aug 17;13(1):139
dc.identifier.uri http://hdl.handle.net/10138/238736
dc.description.abstract Abstract Background The telomere biology disorders (TBDs) include a range of multisystem diseases characterized by mucocutaneous symptoms and bone marrow failure. In dyskeratosis congenita (DKC), the clinical features of TBDs stem from the depletion of crucial stem cell populations in highly proliferative tissues, resulting from abnormal telomerase function. Due to the wide spectrum of clinical presentations and lack of a conclusive laboratory test it may be challenging to reach a clinical diagnosis, especially if patients lack the pathognomonic clinical features of TBDs. Methods Clinical sequencing was performed on a cohort of patients presenting with variable immune phenotypes lacking molecular diagnoses. Hypothesis-free whole-exome sequencing (WES) was selected in the absence of compelling diagnostic hints in patients with variable immunological and haematological conditions. Results In four patients belonging to three families, we have detected five novel variants in known TBD-causing genes (DKC1, TERT and RTEL1). In addition to the molecular findings, they all presented shortened blood cell telomeres. These findings are consistent with the displayed TBD phenotypes, addressing towards the molecular diagnosis and subsequent clinical follow-up of the patients. Conclusions Our results strongly support the utility of WES-based approaches for routine genetic diagnostics of TBD patients with heterogeneous or atypical clinical presentation who otherwise might remain undiagnosed.
dc.publisher BioMed Central
dc.subject Telomere biology disorders,Telomeropathies
dc.subject Next-generation sequencing
dc.subject Whole-exome sequencing
dc.subject Dyskeratosis congenita
dc.subject DKC1; TERT; RTEL1
dc.title Diagnostics of rare disorders: whole-exome sequencing deciphering locus heterogeneity in telomere biology disorders
dc.date.updated 2018-08-19T03:24:32Z
dc.language.rfc3066 en
dc.rights.holder The Author(s).
dc.type.uri http://purl.org/eprint/entityType/ScholarlyWork
dc.type.uri http://purl.org/eprint/entityType/Expression
dc.type.uri http://purl.org/eprint/type/JournalArticle

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