KDF1, encoding keratinocyte differentiation factor 1, is mutated in a multigenerational family with ectodermal dysplasia
Type
ArticleAuthors
Shamseldin, Hanan E.Khalifa, Ola
Binamer, Yousef M.
Almutawa, Abdulmonem
Arold, Stefan T.

Zaidan, Hamad
Alkuraya, Fowzan S.

KAUST Department
Biological and Environmental Sciences and Engineering (BESE) DivisionBioscience Program
Computational Bioscience Research Center (CBRC)
Date
2016-11-12Online Publication Date
2016-11-12Print Publication Date
2017-01Permanent link to this record
http://hdl.handle.net/10754/622158
Metadata
Show full item recordAbstract
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.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.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).Publisher
Springer NatureJournal
Human GeneticsAdditional Links
http://link.springer.com/article/10.1007%2Fs00439-016-1741-zae974a485f413a2113503eed53cd6c53
10.1007/s00439-016-1741-z