title: KDF1, encoding keratinocyte differentiation factor 1, is mutated in a multigenerational family with ectodermal dysplasia.
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.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Hanan E
authors.initials: HE
authors.lastname: Shamseldin
authors.affiliation: Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.|Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Ola
authors.initials: O
authors.lastname: Khalifa
authors.affiliation: Department of Dermatology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Yousef M
authors.initials: YM
authors.lastname: Binamer
authors.affiliation: Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia.
authors.forename: Abdulmonem
authors.initials: A
authors.lastname: Almutawa
authors.affiliation: Division of Biological and Environmental Sciences and Engineering (BESE), Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.
authors.forename: Stefan T
authors.initials: ST
authors.lastname: Arold
authors.affiliation: Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. hzaidan@kfshrc.edu.sa.
authors.forename: Hamad
authors.initials: H
authors.lastname: Zaidan
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.|Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002874:Chromosome Mapping; D019295:Computational Biology; D004195:Disease Models, Animal; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D015603:Keratinocytes / Q000166:cytology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: C585111:KDF1 protein, mouse; D011506:Proteins