KDF1, Encoding Keratinocyte Differentiation Factor 1, is Mutated in a Multigenerational Family with Ectodermal Dysplasia

Overview

Journal Hum Genet

Specialty Genetics

Date 2016 Nov 14

PMID 27838789

Citations 15

Authors

Hanan E Shamseldin

Ola Khalifa

Yousef M Binamer

Abdulmonem Almutawa

Stefan T Arold

Hamad Zaidan

Fowzan S Alkuraya

Affiliations

Soon will be listed here.

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.

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References

Guenet J, SALZGEBER B, Tassin M . Repeated epilation: a genetic epidermal syndrome in mice. J Hered. 1979; 70(2):90-4. DOI: 10.1093/oxfordjournals.jhered.a109223. View

Fomenkov A, Zangen R, Huang Y, Osada M, Guo Z, Fomenkov T . RACK1 and stratifin target DeltaNp63alpha for a proteasome degradation in head and neck squamous cell carcinoma cells upon DNA damage. Cell Cycle. 2004; 3(10):1285-95. DOI: 10.4161/cc.3.10.1155. View

Holbrook K, Dale B, Brown K . Abnormal epidermal keratinization in the repeated epilation mutant mouse. J Cell Biol. 1982; 92(2):387-97. PMC: 2112075. DOI: 10.1083/jcb.92.2.387. View

Prasad G, Valverius E, McDuffie E, Cooper H . Complementary DNA cloning of a novel epithelial cell marker protein, HME1, that may be down-regulated in neoplastic mammary cells. Cell Growth Differ. 1992; 3(8):507-13. View

Koster M, Roop D . The role of p63 in development and differentiation of the epidermis. J Dermatol Sci. 2004; 34(1):3-9. DOI: 10.1016/j.jdermsci.2003.10.003. View

Arnold K, Bordoli L, Kopp J, Schwede T . The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics. 2005; 22(2):195-201. DOI: 10.1093/bioinformatics/bti770. View

Li Q, Sambandam S, Lu H, Thomson A, Kim S, Lu H . 14-3-3σ and p63 play opposing roles in epidermal tumorigenesis. Carcinogenesis. 2011; 32(12):1782-8. PMC: 3220605. DOI: 10.1093/carcin/bgr207. View

Niemann C, Watt F . Designer skin: lineage commitment in postnatal epidermis. Trends Cell Biol. 2002; 12(4):185-92. DOI: 10.1016/s0962-8924(02)02263-8. View

Mitchell K, OSullivan J, Missero C, Blair E, Richardson R, Anderson B . Exome sequence identifies RIPK4 as the Bartsocas-Papas syndrome locus. Am J Hum Genet. 2011; 90(1):69-75. PMC: 3257958. DOI: 10.1016/j.ajhg.2011.11.013. View

10.

Shamseldin H, Maddirevula S, Faqeih E, Ibrahim N, Hashem M, Shaheen R . Increasing the sensitivity of clinical exome sequencing through improved filtration strategy. Genet Med. 2016; 19(5):593-598. DOI: 10.1038/gim.2016.155. View

11.

Koster M, Kim S, Mills A, DeMayo F, Roop D . p63 is the molecular switch for initiation of an epithelial stratification program. Genes Dev. 2004; 18(2):126-31. PMC: 324418. DOI: 10.1101/gad.1165104. View

12.

Kall L, Krogh A, Sonnhammer E . A combined transmembrane topology and signal peptide prediction method. J Mol Biol. 2004; 338(5):1027-36. DOI: 10.1016/j.jmb.2004.03.016. View

13.

Herron B, Liddell R, Parker A, Grant S, Kinne J, Fisher J . A mutation in stratifin is responsible for the repeated epilation (Er) phenotype in mice. Nat Genet. 2005; 37(11):1210-2. DOI: 10.1038/ng1652. View

14.

Doffinger R, Smahi A, Bessia C, Geissmann F, Feinberg J, Durandy A . X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nat Genet. 2001; 27(3):277-85. DOI: 10.1038/85837. View

15.

Shaheen R, Ansari S, Alshammari M, Alkhalidi H, Alrukban H, Eyaid W . A novel syndrome of hypohidrosis and intellectual disability is linked to COG6 deficiency. J Med Genet. 2013; 50(7):431-6. DOI: 10.1136/jmedgenet-2013-101527. View

16.

Li Q, Lu Q, Estepa G, Verma I . Identification of 14-3-3sigma mutation causing cutaneous abnormality in repeated-epilation mutant mouse. Proc Natl Acad Sci U S A. 2005; 102(44):15977-82. PMC: 1276109. DOI: 10.1073/pnas.0508310102. View

17.

Milstone L . Epidermal desquamation. J Dermatol Sci. 2004; 36(3):131-40. DOI: 10.1016/j.jdermsci.2004.05.004. View

18.

Fuchs E . Epidermal differentiation: the bare essentials. J Cell Biol. 1990; 111(6 Pt 2):2807-14. PMC: 2116387. DOI: 10.1083/jcb.111.6.2807. View

19.

Xu D, Zhang Y . Ab initio protein structure assembly using continuous structure fragments and optimized knowledge-based force field. Proteins. 2012; 80(7):1715-35. PMC: 3370074. DOI: 10.1002/prot.24065. View

20.

Koster M . p63 in skin development and ectodermal dysplasias. J Invest Dermatol. 2010; 130(10):2352-8. PMC: 2919658. DOI: 10.1038/jid.2010.119. View