The mutation spectrum of the EDA gene in X-linked anhidrotic ectodermal dysplasia

✍ Scribed by Kati Pääkkönen; Stefano Cambiaghi; Giuseppe Novelli; Lizbeth V. Ouzts; Maila Penttinen; Juha Kere; Anand K. Srivastava

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 84 KB
• Volume: 17
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.33

✦ Synopsis

Communicated by Uta Francke

Mutations in ectodysplasin, the protein product of the EDA or ED1 gene, cause X-linked anhidrotic ectodermal dysplasia. From sixteen families we have identified thirteen mutations, of which nine were novel: a deletion of the entire exon 1, altered splicing site in intron 7 (IVS7-2Aà à G) and in intron 9 (IVS9+8 Cà à G), deletion of 8 bp (1967-1974 nt), four missense mutations (G255C, G255D, W274G, C332Y) and nonsense mutation W274X. Previously identified and the novel mutations form four clusters: 1) at the junction of the transmembrane and extracellular domains, 2) at a putative protease recognition site, possibly affecting cleavage of ectodysplasin, 3) at the trimerizing collagen-like domain, and 4) at regions of high homology to tumor necrosis factor domains. Truncating and splice site mutations occur within the proximal two-thirds of the protein. Our data suggest the functional importance of specific ectodysplasin domains.