Mutation p.Leu354Pro in EDA causes severe hypohidrotic ectodermal dysplasia in a Chinese family.
X-linked recessive hypohidrotic ectodermal dysplasia (XLHED) is characterized by the defective morphogenesis of teeth, hair, and eccrine sweat glands. It is associated with mutations in the EDA gene. Up to now, more than 100 mutations in the EDA gene have been reported to cause XLHED. The product of EDA gene is a trimeric type II transmembrane protein that belongs to the tumor necrosis factor (TNF) family of ligands. In this study, we identified a Chinese family with XLHED. Direct DNA sequencing of the whole coding region of EDA revealed a novel missense mutation, p.Leu354Pro in a patient affected with XLHED. This mutation was not found in either unaffected male individuals of the family or 168 normal controls. The substitution of Leu354 with Pro was found to be located in the TNF-like domain of EDA and may influence the epithelial signaling pathway required for the normal ectodermal development through altering the topology of EDA. Our finding broadens the spectrum of EDA mutations and may help to understand the molecular basis of XLHED and aid genetic counseling.
Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, PR China.
Ying
Y
Liu
Xiaoyan
X
Yu
Lei
L
Wang
Chang
C
Li
Stephen
S
Archacki
Changzheng
C
Huang
Jing Yu
JY
Liu
Qing
Q
Wang
Mugen
M
Liu
Zhaohui
Z
Tang
D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002648:Child; D053358:Ectodermal Dysplasia 1, Anhidrotic / Q000235:genetics*; D053331:Ectodysplasins / Q000235:genetics*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D020125:Mutation, Missense; D010375:Pedigree
C506018:EDA protein, human; D053331:Ectodysplasins