Publication:
Identification of likely pathogenic and known variants in TSPEAR, LAMB3, BCOR, and WNT10A in four Turkish families with tooth agenesis

dc.contributor.coauthorDu, Renqian
dc.contributor.coauthorDinckan, Nuriye
dc.contributor.coauthorSong, Xiaofei
dc.contributor.coauthorCoban-Akdemir, Zeynep
dc.contributor.coauthorJhangiani, Shalini N.
dc.contributor.coauthorGuven, Yeliz
dc.contributor.coauthorAktoren, Oya
dc.contributor.coauthorPetty, Lauren E.
dc.contributor.coauthorMuzny, Donna M.
dc.contributor.coauthorBelow, Jennifer E.
dc.contributor.coauthorBoerwinkle, Eric
dc.contributor.coauthorWu, Nan
dc.contributor.coauthorGibbs, Richard A.
dc.contributor.coauthorPosey, Jennifer E.
dc.contributor.coauthorLupski, James R.
dc.contributor.coauthorLetra, Ariadne
dc.contributor.coauthorUyguner, Z. Oya
dc.contributor.departmentSchool of Medicine
dc.contributor.kuauthorKayserili, Hülya
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2024-11-09T23:19:17Z
dc.date.issued2018
dc.description.abstractTooth agenesis (TA), the failure of development of one or more permanent teeth, is a common craniofacial abnormality observed in different world populations. The genetic etiology of TA is heterogeneous; more than a dozen genes have been associated with isolated or nonsyndromic TA, and more than 80 genes with syndromic forms. In this study, we applied whole exome sequencing (WES) to identify candidate genes contributing to TA in four Turkish families. Likely pathogenic variants with a low allele frequency in the general population were identified in four disease-associated genes, including two distinct variants in TSPEAR, associated with syndromic and isolated TA in one family each; a variant in LAMB3 associated with syndromic TA in one family; and a variant in BCOR plus a disease-associated WNT10A variant in one family with syndromic TA. With the notable exception of WNT10A (Tooth agenesis, selective, 4, MIM #150400), the genotype-phenotype relationships described in the present cohort represent an expansion of the clinical spectrum associated with these genes: TSPEAR (Deafness, autosomal recessive 98, MIM #614861), LAMB3 (Amelogenesis imperfecta, type IA, MIM #104530; Epidermolysis bullosa, junctional, MIMs #226700 and #226650), and BCOR (Microphthalmia, syndromic 2, MIM #300166). We provide evidence supporting the candidacy of these genes with TA, and propose TSPEAR as a novel nonsyndromic TA gene. Our data also suggest potential multilocus genomic variation, or mutational burden, in a single family, involving the BCOR and WNT10A loci, underscoring the complexity of the genotype-phenotype relationship in the common complex trait of TA.
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue9
dc.description.openaccessYES
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipScientific and Technological Research Institution of Turkey, TUBITAK-ERA NET (CRANIRARE-2) [SBAG-112S398]
dc.description.sponsorshipIstanbul University Research Fund [48398]
dc.description.sponsorshipNational Institute of Dental and Craniofacial Research (NIDCR) [R03-DE024596]
dc.description.sponsorshipBaylor-Hopkins Center for Mendelian Genomics, BHCMG [UM1 HG006542]
dc.description.sponsorshipNational Human Genome Research Institute (NHGRI)
dc.description.sponsorshipNational Heart Lung and Blood Institute (NHLBI)
dc.description.sponsorshipNHGRI [K08 HG008986]
dc.description.sponsorshipMilstein Medical Asian American Partnership Foundation Fellowship Award in Translational Medicine
dc.description.sponsorship[U24 HG008956] We appreciate the participation of the patients and their families in this project. We also thank Dr. Ousheng Liu and Dr. Davut Pehlivan for helpful discussions. This work was supported in part by the Scientific and Technological Research Institution of Turkey, TUBITAK-ERA NET (CRANIRARE-2, grant number: SBAG-112S398), Istanbul University Research Fund (Project No: 48398), National Institute of Dental and Craniofacial Research (NIDCR) R03-DE024596 (to AL) and the Baylor-Hopkins Center for Mendelian Genomics, BHCMG (UM1 HG006542, to JRL). The BHCMG is jointly funded by the National Human Genome Research Institute (NHGRI) and National Heart Lung and Blood Institute (NHLBI). The GSP Coordinating Center (U24 HG008956) contributed to cross-program scientific initiatives and provided logistical and general study coordination. JEP was supported by NHGRI K08 HG008986. NW was supported by 2016 Milstein Medical Asian American Partnership Foundation Fellowship Award in Translational Medicine.
dc.description.volume137
dc.identifier.doi10.1007/s00439-018-1907-y
dc.identifier.eissn1432-1203
dc.identifier.issn0340-6717
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-85050675545
dc.identifier.urihttps://doi.org/10.1007/s00439-018-1907-y
dc.identifier.urihttps://hdl.handle.net/20.500.14288/10526
dc.identifier.wos444822200003
dc.keywordsDominant
dc.keywordsGene
dc.keywordsHerlitz
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofHuman Genetics
dc.subjectGenetics
dc.subjectHeredity
dc.titleIdentification of likely pathogenic and known variants in TSPEAR, LAMB3, BCOR, and WNT10A in four Turkish families with tooth agenesis
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorKayserili, Hülya
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit2School of Medicine
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relation.isParentOrgUnitOfPublication17f2dc8e-6e54-4fa8-b5e0-d6415123a93e
relation.isParentOrgUnitOfPublication.latestForDiscovery17f2dc8e-6e54-4fa8-b5e0-d6415123a93e

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