The mutation spectrum of the EDA gene in X-linked anhidrotic ectodermal dysplasia.
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 (IVS-2A-->G) and in intron 9 (IVS9+8 C-->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. Hum Mutat 17:349, 2001.
Pääkkönen
K
K
Department of Medical Genetics, Haartman Institute, PO Box 21, University of Helsinki, FIN-00014 Helsinki, Finland.
Cambiaghi
S
S
Novelli
G
G
Ouzts
L V
LV
Penttinen
M
M
Kere
J
J
Srivastava
A K
AK
D017398:Alternative Splicing / Q000235:genetics; D020816:Amino Acid Motifs; D004252:DNA Mutational Analysis; D004476:Ectodermal Dysplasia / Q000235:genetics* / Q000503:physiopathology; D053331:Ectodysplasins; D005091:Exons / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D017434:Protein Structure, Tertiary; D022821:RNA Splice Sites / Q000235:genetics; D014960:X Chromosome / Q000235:genetics*
C506018:EDA protein, human; D053331:Ectodysplasins; D008565:Membrane Proteins; D022821:RNA Splice Sites