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

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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

Title: Diagnostics of rare disorders : whole-exome sequencing deciphering locus heterogeneity in telomere biology disorders
Author: Trotta, Luca; Norberg, Anna; Taskinen, Mervi; Beziat, Vivien; Degerman, Sofie; Wartiovaara-Kautto, Ulla; Välimaa, Hannamari; Jahnukainen, Kirsi; Casanova, Jean-Laurent; Seppänen, Mikko; Saarela, Janna; Koskenvuo, Minna; Martelius, Timi
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Lastentautien yksikkö
University of Helsinki, Clinicum
University of Helsinki, Medicum
University of Helsinki, Doctoral Programme in Clinical Research
University of Helsinki, Children's Hospital
University of Helsinki, Doctoral Programme in Integrative Life Science
University of Helsinki, Clinicum
University of Helsinki, Infektiosairauksien yksikkö
Date: 2018-08-17
Language: eng
Number of pages: 9
Belongs to series: Orphanet journal of rare diseases
ISSN: 1750-1172
URI: http://hdl.handle.net/10138/243577
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.
Subject: Telomere biology disorders
Telomeropathies
Next-generation sequencing
Whole-exome sequencing
Dyskeratosis congenita
DKC1
TERT
RTEL1
HOYERAAL-HREIDARSSON SYNDROME
BURROWS-WHEELER TRANSFORM
DYSKERATOSIS-CONGENITA
MOLECULAR-GENETICS
READ ALIGNMENT
MUTATIONS
VARIANTS
3121 General medicine, internal medicine and other clinical medicine
3111 Biomedicine
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