A rare case of hypohidrotic ectodermal dysplasia caused by compound heterozygous mutations in the EDAR gene

被引:31
|
作者
Shimomura, Y [1 ]
Sato, N
Miyashita, A
Hashimoto, T
Ito, M
Kuwano, R
机构
[1] Niigata Univ, Sch Med, Dept Dermatol, Niigata 9518510, Japan
[2] Niigata Univ, Brain Res Inst, Dept Mol Genet, Genome Sci Branch,Ctr Bioresource Based Res, Niigata, Japan
关键词
compound heterozygous mutations; death domain; EDAR gene; hypohidrotic ectodermal dysplasia;
D O I
10.1111/j.0022-202X.2004.23405.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Hypohidrotic ectodermal dysplasia (HED) is a genetic disease characterized by abnormal hair, teeth, and sweat gland development. Although most cases of HED display X-linked recessive inheritance, autosomal dominant and autosomal recessive forms also exist. X-linked HED is caused by mutations in the EDA gene, and the autosomal forms result from mutations in either the EDAR gene or the EDARADD gene. In this study, we identified compound heterozygous mutations in the EDAR gene in a Japanese female patient with HED. On the maternal allele is a novel splice donor site mutation of intron 2 leading to the generation of unstable transcripts with exon 2 skipping; on the paternal allele is a novel R375H transition within the death domain of EDAR. Using expression studies in tissue culture cells, we found that the R375H substitution in EDAR caused loss of its affinity for EDARADD and reduced activation of the downstream target NF-kappaB. Our findings indicate that both alleles of EDAR are non-functional in our patient, resulting in the HED phenotype.
引用
收藏
页码:649 / 655
页数:7
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