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 Beziat, 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 2018-09-19T07:24:01Z
dc.date.available 2018-09-19T07:24:01Z
dc.date.issued 2018-08-17
dc.identifier.citation Trotta , L , Norberg , A , Taskinen , M , Beziat , V , Degerman , S , Wartiovaara-Kautto , U , Välimaa , H , Jahnukainen , K , Casanova , J-L , Seppänen , M , Saarela , J , Koskenvuo , M & Martelius , T 2018 , ' Diagnostics of rare disorders : whole-exome sequencing deciphering locus heterogeneity in telomere biology disorders ' , Orphanet journal of rare diseases , vol. 13 , 139 . https://doi.org/10.1186/s13023-018-0864-9
dc.identifier.other PURE: 115652303
dc.identifier.other PURE UUID: 03da36bc-428a-45e2-afda-748654a48c91
dc.identifier.other WOS: 000442134700001
dc.identifier.other Scopus: 85051726365
dc.identifier.other ORCID: /0000-0002-0853-6219/work/48610027
dc.identifier.other ORCID: /0000-0001-9733-3650/work/48611859
dc.identifier.uri http://hdl.handle.net/10138/243577
dc.description.abstract Background: The telomere biology disorders (TBDs) include a range of multisystem diseases characterized by mucocutaneous symptoms and bone marrow failure. In dyskeratosis congenita (DKQ, 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. en
dc.format.extent 9
dc.language.iso eng
dc.relation.ispartof Orphanet journal of rare diseases
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject Telomere biology disorders
dc.subject Telomeropathies
dc.subject Next-generation sequencing
dc.subject Whole-exome sequencing
dc.subject Dyskeratosis congenita
dc.subject DKC1
dc.subject TERT
dc.subject RTEL1
dc.subject MUTATIONS
dc.subject VARIANTS
dc.subject 3121 General medicine, internal medicine and other clinical medicine
dc.subject 3111 Biomedicine
dc.title Diagnostics of rare disorders : whole-exome sequencing deciphering locus heterogeneity in telomere biology disorders en
dc.type Article
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization Helsinki Institute of Life Science HiLIFE
dc.contributor.organization University of Helsinki
dc.contributor.organization Lastentautien yksikkö
dc.contributor.organization Children's Hospital
dc.contributor.organization Clinicum
dc.contributor.organization Department of Oncology
dc.contributor.organization Hematologian yksikkö
dc.contributor.organization Medicum
dc.contributor.organization Department of Virology
dc.contributor.organization Oral and Maxillofacial Surgery
dc.contributor.organization Doctoral Programme in Clinical Research
dc.contributor.organization Department of Medicine
dc.contributor.organization Infektiosairauksien yksikkö
dc.contributor.organization Doctoral Programme in Integrative Life Science
dc.contributor.organization Janna Saarela / Principal Investigator
dc.contributor.organization HUS Children and Adolescents
dc.contributor.organization HUS Comprehensive Cancer Center
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1186/s13023-018-0864-9
dc.relation.issn 1750-1172
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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