KDF1, encoding keratinocyte differentiation factor 1, is mutated in a multigenerational family with ectodermal dysplasia

Handle URI:
http://hdl.handle.net/10754/622158
Title:
KDF1, encoding keratinocyte differentiation factor 1, is mutated in a multigenerational family with ectodermal dysplasia
Authors:
Shamseldin, Hanan E.; Khalifa, Ola; Binamer, Yousef M.; Almutawa, Abdulmonem; Arold, Stefan T. ( 0000-0001-5278-0668 ) ; Zaidan, Hamad; Alkuraya, Fowzan S.
Abstract:
Ectodermal dysplasia is a highly heterogeneous group of disorders that variably affect the derivatives of the ectoderm, primarily skin, hair, nails and teeth. TP63, itself mutated in ectodermal dysplasia, links many other ectodermal dysplasia disease genes through a regulatory network that maintains the balance between proliferation and differentiation of the epidermis and other ectodermal derivatives. The ectodermal knockout phenotype of five mouse genes that regulate and/or are regulated by TP63 (Irf6, Ikkα, Ripk4, Stratifin, and Kdf1) is strikingly similar and involves abnormal balance towards proliferation at the expense of differentiation, but only the first three have corresponding ectodermal phenotypes in humans. We describe a multigenerational Saudi family with an autosomal dominant form of hypohidrotic ectodermal dysplasia in which positional mapping and exome sequencing identified a novel variant in KDF1 that fully segregates with the phenotype. The recapitulation of the phenotype we observe in this family by the Kdf1−/− mouse suggests a causal role played by the KDF1 variant.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Computational Bioscience Research Center (CBRC)
Citation:
Shamseldin HE, Khalifa O, Binamer YM, Almutawa A, Arold ST, et al. (2016) KDF1, encoding keratinocyte differentiation factor 1, is mutated in a multigenerational family with ectodermal dysplasia. Human Genetics. Available: http://dx.doi.org/10.1007/s00439-016-1741-z.
Publisher:
Springer Nature
Journal:
Human Genetics
Issue Date:
12-Nov-2016
DOI:
10.1007/s00439-016-1741-z
Type:
Article
ISSN:
0340-6717; 1432-1203
Sponsors:
We thank the study family for their enthusiastic participation. We also thank the Sequencing and Genotyping Core Facilities at KFSHRC for their technical help. This work was supported by KACST Grant 13-BIO1113-20 (FSA) and King Abdullah University of Science and Technology (KAUST) (STA).
Additional Links:
http://link.springer.com/article/10.1007%2Fs00439-016-1741-z
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorShamseldin, Hanan E.en
dc.contributor.authorKhalifa, Olaen
dc.contributor.authorBinamer, Yousef M.en
dc.contributor.authorAlmutawa, Abdulmonemen
dc.contributor.authorArold, Stefan T.en
dc.contributor.authorZaidan, Hamaden
dc.contributor.authorAlkuraya, Fowzan S.en
dc.date.accessioned2017-01-02T08:42:34Z-
dc.date.available2017-01-02T08:42:34Z-
dc.date.issued2016-11-12en
dc.identifier.citationShamseldin HE, Khalifa O, Binamer YM, Almutawa A, Arold ST, et al. (2016) KDF1, encoding keratinocyte differentiation factor 1, is mutated in a multigenerational family with ectodermal dysplasia. Human Genetics. Available: http://dx.doi.org/10.1007/s00439-016-1741-z.en
dc.identifier.issn0340-6717en
dc.identifier.issn1432-1203en
dc.identifier.doi10.1007/s00439-016-1741-zen
dc.identifier.urihttp://hdl.handle.net/10754/622158-
dc.description.abstractEctodermal dysplasia is a highly heterogeneous group of disorders that variably affect the derivatives of the ectoderm, primarily skin, hair, nails and teeth. TP63, itself mutated in ectodermal dysplasia, links many other ectodermal dysplasia disease genes through a regulatory network that maintains the balance between proliferation and differentiation of the epidermis and other ectodermal derivatives. The ectodermal knockout phenotype of five mouse genes that regulate and/or are regulated by TP63 (Irf6, Ikkα, Ripk4, Stratifin, and Kdf1) is strikingly similar and involves abnormal balance towards proliferation at the expense of differentiation, but only the first three have corresponding ectodermal phenotypes in humans. We describe a multigenerational Saudi family with an autosomal dominant form of hypohidrotic ectodermal dysplasia in which positional mapping and exome sequencing identified a novel variant in KDF1 that fully segregates with the phenotype. The recapitulation of the phenotype we observe in this family by the Kdf1−/− mouse suggests a causal role played by the KDF1 variant.en
dc.description.sponsorshipWe thank the study family for their enthusiastic participation. We also thank the Sequencing and Genotyping Core Facilities at KFSHRC for their technical help. This work was supported by KACST Grant 13-BIO1113-20 (FSA) and King Abdullah University of Science and Technology (KAUST) (STA).en
dc.publisherSpringer Natureen
dc.relation.urlhttp://link.springer.com/article/10.1007%2Fs00439-016-1741-zen
dc.titleKDF1, encoding keratinocyte differentiation factor 1, is mutated in a multigenerational family with ectodermal dysplasiaen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalHuman Geneticsen
dc.contributor.institutionDepartment of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabiaen
dc.contributor.institutionDepartment of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabiaen
dc.contributor.institutionDepartment of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypten
dc.contributor.institutionDepartment of Dermatology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabiaen
dc.contributor.institutionDepartment of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabiaen
dc.contributor.institutionDepartment of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabiaen
kaust.authorArold, Stefan T.en
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