Marked overlap of four genetic syndromes with dyskeratosis congenita confounds clinical diagnosis
dc.contributor.author | Walne, Amanda J. | |
dc.contributor.author | Collopy, Laura | |
dc.contributor.author | Cardoso, Shirleny | |
dc.contributor.author | Ellison, Alicia | |
dc.contributor.author | Plagnol, Vincent | |
dc.contributor.author | Albayrak, Canan | |
dc.contributor.author | Albayrak, Davut | |
dc.contributor.author | Patiroğlu, Türkan | |
dc.contributor.author | Akar, Haluk | |
dc.contributor.author | Godfrey, Keith | |
dc.contributor.author | Carter, Tina | |
dc.contributor.author | Marafie, Makia | |
dc.contributor.author | Vora, Ajay | |
dc.contributor.author | Sundin, Mikael | |
dc.contributor.author | Vulliamy, Thomas | |
dc.contributor.author | Tummala, Hemanth | |
dc.contributor.author | Dokal, Inderjeet | |
dc.contributor.buuauthor | Kılıç, Sara Şebnem | |
dc.contributor.department | Uludağ Üniversitesi/Tıp Fakültesi/Çocuk İmmünolojisi Anabilim Dalı. | tr_TR |
dc.contributor.orcid | 0000-0001-8571-2581 | tr_TR |
dc.contributor.researcherid | AAH-1658-2021 | tr_TR |
dc.contributor.scopusid | 34975059200 | tr_TR |
dc.date.accessioned | 2022-10-26T08:27:12Z | |
dc.date.available | 2022-10-26T08:27:12Z | |
dc.date.issued | 2016-06-21 | |
dc.description.abstract | Dyskeratosis congenita is a highly pleotropic genetic disorder. This heterogeneity can lead to difficulties in making an accurate diagnosis and delays in appropriate management. The aim of this study was to determine the underlying genetic basis in patients presenting with features of dyskeratosis congenita and who were negative for mutations in the classical dyskeratosis congenita genes. By whole exome and targeted sequencing, we identified biallelic variants in genes that are not associated with dyskeratosis congenita in 17 individuals from 12 families. Specifically, these were homozygous variants in USB1 (8 families), homozygous missense variants in GRHL2 (2 families) and identical compound heterozygous variants in LIG4 (2 families). All patients had multiple somatic features of dyskeratosis congenita but not the characteristic short telomeres. Our case series shows that biallelic variants in USB1, LIG4 and GRHL2, the genes mutated in poikiloderma with neutropenia, LIG4/Dubowitz syndrome and the recently recognized ectodermal dysplasia/short stature syndrome, respectively, cause features that overlap with dyskeratosis congenita. Strikingly, these genes also overlap in their biological function with the known dyskeratosis congenita genes that are implicated in telomere maintenance and DNA repair pathways. Collectively, these observations demonstrate the marked overlap of dyskeratosis congenita with four other genetic syndromes, confounding accurate diagnosis and subsequent management. This has important implications for establishing a genetic diagnosis when a new patient presents in the clinic. Patients with clinical features of dyskeratosis congenita need to have genetic analysis of USB1, LIG4 and GRHL2 in addition to the classical dyskeratosis congenita genes and telomere length measurements. | en_US |
dc.description.sponsorship | UK Research & Innovation (UKRI) | en_US |
dc.description.sponsorship | Medical Research Council UK (MRC) - MR/K000292/1 | en_US |
dc.description.sponsorship | European Commission - MC_UU_12011/4 | en_US |
dc.description.sponsorship | Children with Cancer - 2013/144 | en_US |
dc.description.sponsorship | Blood Wise - 14032 | en_US |
dc.description.sponsorship | National Institute for Health Research through the NIHR Southampton Biomedical Research Centre | en_US |
dc.description.sponsorship | National Institute for Health Research (NIHR) - NF-SI-0515-10042 | en_US |
dc.description.sponsorship | UK Research & Innovation (UKRI) - MR/K000292/1 | en_US |
dc.description.sponsorship | Medical Research Council UK (MRC) | en_US |
dc.identifier.citation | Walne, A. J. vd. (2016). "Marked overlap of four genetic syndromes with dyskeratosis congenita confounds clinical diagnosis". Haematologica, 101(10), 1180-1189. | en_US |
dc.identifier.endpage | 1189 | tr_TR |
dc.identifier.issn | 0390-6078 | |
dc.identifier.issue | 10 | tr_TR |
dc.identifier.pubmed | 27612988 | tr_TR |
dc.identifier.scopus | 2-s2.0-84989282799 | tr_TR |
dc.identifier.startpage | 1180 | tr_TR |
dc.identifier.uri | https://doi.org/10.3324/haematol.2016.147769 | |
dc.identifier.uri | https://haematologica.org/article/view/7844 | |
dc.identifier.uri | http://hdl.handle.net/11452/29214 | |
dc.identifier.volume | 101 | tr_TR |
dc.identifier.wos | 000392548700019 | tr_TR |
dc.indexed.pubmed | PubMed | en_US |
dc.indexed.scopus | Scopus | en_US |
dc.indexed.wos | SCIE | en_US |
dc.language.iso | en | en_US |
dc.publisher | Ferrata Storti Foundation | en_US |
dc.relation.collaboration | Yurt içi | tr_TR |
dc.relation.collaboration | Yurt dışı | tr_TR |
dc.relation.collaboration | Sanayi | tr_TR |
dc.relation.journal | Haematologica | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi | tr_TR |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.subject | Hematology | en_US |
dc.subject | Bone-marrow failure | en_US |
dc.subject | Telomere biology | en_US |
dc.subject | Poikiloderma | en_US |
dc.subject | Mutations | en_US |
dc.subject | Neutropenia | en_US |
dc.subject | C16orf57 | en_US |
dc.subject | Length | en_US |
dc.subject | Maturation | en_US |
dc.subject | Family | en_US |
dc.subject | Grhl2 | en_US |
dc.subject.emtree | ATP dependent DNA ligase | en_US |
dc.subject.emtree | DNA binding protein | en_US |
dc.subject.emtree | GRHL2 protein, human | en_US |
dc.subject.emtree | LIG4 protein, human | en_US |
dc.subject.emtree | Phosphodiesterase | en_US |
dc.subject.emtree | Transcription factor | en_US |
dc.subject.emtree | USB1 protein, human | en_US |
dc.subject.emtree | 5' untranslated region | en_US |
dc.subject.emtree | Article | en_US |
dc.subject.emtree | Cell proliferation | en_US |
dc.subject.emtree | DNA repair | en_US |
dc.subject.emtree | Dyskeratosis congenita | en_US |
dc.subject.emtree | Gene | en_US |
dc.subject.emtree | Genetic analysis | en_US |
dc.subject.emtree | Genetic disorder | en_US |
dc.subject.emtree | GRHL2 gene | en_US |
dc.subject.emtree | LIG4 gene | en_US |
dc.subject.emtree | Nail dystrophy | en_US |
dc.subject.emtree | Neutropenia | en_US |
dc.subject.emtree | Poikiloderma | en_US |
dc.subject.emtree | Polymerase chain reaction | en_US |
dc.subject.emtree | Segregation analysis | en_US |
dc.subject.emtree | Telomere homeostasis | en_US |
dc.subject.emtree | USB1 gene | en_US |
dc.subject.emtree | DNA sequence | en_US |
dc.subject.emtree | Dyskeratosis congenita | en_US |
dc.subject.emtree | Exome | en_US |
dc.subject.emtree | Genetic variation | en_US |
dc.subject.emtree | Genetics | en_US |
dc.subject.emtree | Human | en_US |
dc.subject.emtree | Pedigree | en_US |
dc.subject.emtree | Syndrome | en_US |
dc.subject.mesh | DNA ligase ATP | en_US |
dc.subject.mesh | DNA-binding proteins | en_US |
dc.subject.mesh | Dyskeratosis congenita | en_US |
dc.subject.mesh | Exome | en_US |
dc.subject.mesh | Genetic variation | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Pedigree | en_US |
dc.subject.mesh | Phosphoric diester hydrolases | en_US |
dc.subject.mesh | Sequence analysis, DNA | en_US |
dc.subject.mesh | Syndrome | en_US |
dc.subject.mesh | Transcription factors | en_US |
dc.subject.scopus | Dyskeratosis Congenita; Mutation; Telomerase RNA | en_US |
dc.subject.wos | Hematology | en_US |
dc.title | Marked overlap of four genetic syndromes with dyskeratosis congenita confounds clinical diagnosis | en_US |
dc.type | Article | |
dc.wos.quartile | Q1 | en_US |