A Novel Ectodysplasin a Gene mutation of X-Linked Hypohidrotic Ectodermal Dysplasia

Figures & data

Figure 1 (A) Pedigrees and Sanger sequencing of families with EDA mutation:□, normal male; ○, normal female; ◉, female XLHED carrier; ■, male XLHED patient; the arrow shows the proband; pedigree with those affected shown in black filled symbols. (B) Sequence chromatograms (The Red arrowhead denotes that the novel missensemutationcan Resulting in the replacement of methionine at codon 373 with isoleucine.):(a) Hemizygousmutation. (b) Heterozygous mutation. (c) Normal DNA sequence. (C) Multiple sequence alignment of EDA from a variety of species. The red rectangular frames indicate the locations of M373I.

Figure 2 (A) Real-Time Quantitative PCR:Compared with wild-type EDA, the mutant EDA protein significantly inhibited the expression of EDA level.****means p <0 .0001 (Student t test). (B and C) Protein expression of mutant EDA1 in transfected cell.HEK293T cells were transfected with vectors encoding mutant or wild-type soluble FLAG-tagged EDA1 protein, cell lysates were separately analyzed by western blotting, β-tubulin was used as a loading control. The bands showed that wild-type EDA1 can produce proteins, the weaker bands of p.M373I mutations in the cell lysates showed decreased intracellular protein expression. ****means p <0 .0001 (Student t test).

Figure 3 NF- κB transcriptional activation of mutant EDA. The mutant EDA protein attenuated transcriptionalNF-κB activation compared to wild- type EDA. **means p <0 .05 (Student t test).

Table 1 EDA Gene Mutations Reported as of 2021 According to HGMD Database

Mutation type	Number of mutations reported
Missense/nonsense Small deletions	203 57
Gross deletions	36
Splicing	32
Small insertions	23
Small indels	7
Gross insertions	5
Complex	1
Regulatory	No mutations
Repeats	No mutations

Table 2 Summary of the Clinical Features and Genetic Data of Our Cases and Reported Cases in the Last Five Years

Reference	Variants	Gender	Ethnicity	Hypodontia/Oligodontiateeth	Anhidrosis/Hypohidrosis	Absent/sparse hair	AD/eczema	Dry skin	Ophthalmologic ailments	Mental retardation	Craniofacial abnormalities
Our study	c.1119G>C	Male	Chinese	+	+	+	–	+	–	–	+
doi:10.7717/peerj.3691	c.172–173CA>GG	Male	Chinese	+	+	+	–	–	–	–	Unregistered
doi:10.1111/odi.12376	c.852T>G	Male	Chinese	+	+	+	–	–	–	–	Unregistered
	c.467G>A	Male	Chinese	+	+	+	–	–	–	–	+
	c.776C>A	Male	Chinese	+	–	+	–	–	–	–	Unregistered
	c.871G>A	Male	Chinese	+	+	+	–	–	–	–	Unregistered
doi:10.1159/000500214	c.687delT	Male	Korean	+	+	+	–	–	+	–	+
	c.1133C>A	Male	Korean	+	+	+	+	+	+	–	–
	c.871G>A	Male	Korean	+	+	+	–	+	–	–	+
	c.712delG	Male	Korean	+	+	+	–	+	+	–	+
	c.217G>T	Male	Korean	+	+	+	–	–	+	–	+
	c.463C>T	Female	Korean	+	+	+	–	+	–	+	+
	c.965T>C	Male	Korean	+	+	+	+	+	+	–	–
	c.1045G>A	Male	Korean	+	+	+	+	+	–	–	+
	c.751G>A	Male	Korean	+	–	+	+	–	–	–	–
doi:10.1016/j.archoralbio.2019.104507	c.913A> C	Male	Chinese	+	+	+	–	+	–	–	+
doi:10.3389/fgene.2022.934395	c.924+7A> G	Male	German	+	+	+	+	+	+	–	Unregistered
	c.527G>T	Male	German	+	+	+	+	+	+	–	Unregistered
	c.374C>G	Male	German	+	+	–	+	+	+	–	unregistered
	c.1174T>C	Male	German	+	+	+	–	+	+	–	unregistered
doi:10.1097/MD.0000000000019244	c.1046C>T	Male	Chinese	+	+	+	–	+	–	–	+
	c.146T>A	Male	Chinese	+	+	+	–	+	–	–	+
	c.457C>T	Male	Chinese	+	+	+	–	+	–	–	+
doi:10.3760/cma.j.cn112144-20,210,513-00229	c.2T>C	Male	Chinese	+	+	+	–	+	–	–	+
	c.161A>G	Male	Chinese	+	+	+	+	+	–	–	+
doi:10.1016/j.ymgmr.2021.100796	c.337C>T	Female	American	+	+	+	–	+	–	–	–
doi:10.1089/gtmb.2018.0100	c.466C>T	Male	Chinese	+	+	+	–	+	–	–	+
	c.895G>A	Male	Chinese	+	+	+	–	+	–	–	+
	c.682_683delCCinA	Male	Chinese	+	+	+	–	+	–	–	+
doi:10.3390/diagnostics12102300	c.588_606del19bp	Female	Chinese	+	+	+	–	+	+	–	+
	c.837G>A	Female	Chinese	+	+	+	–	+	+	–	–
doi:10.1186/s13223-021-00510-z	c.766C>T	Male	Italian	+	+	+	+	+	+	–	–
		Female	Italian	+	+	–	–	–	–	–	–
doi:10.1111/odi.12874	c.526+1G>A	Male	Chinese	+	+	+	–	+	+	–	+
doi:10.1111/1346-8138.14252	c.646_681del	Male	Japanese	+	+	+	+	+	+	–	+
doi:10.1002/jcla.22593	c.302_303delCC	Male	Chinese	+	+	+	–	+	–	–	+
doi:10.1111/1346-8138.14978	c.381_382delinsG	Male	Chinese	+	+	+	+	+	+	–	+
		Female	Chinese	+	+	+	+	+	–	–	+
doi:10.4103/ijd.ijd_406_21	c.924+8C>G	Male	Indian	+	–	+	+	+	–	–	+
	c.760C>T	Male	Indian	+	+	+	+	+	–	–	+
doi:10.24875/BMHIM.19000209	c.466C>T	Male	Mexican	+	+	+	–	+	–	–	+
doi:10.1186/s13052-021-01078-5	c.1142G>C	Male	Italian	+	+	+	+	+	+	–	+
doi:10.1186/s11658-019-0174-9	c.898_924+8del35ins4CTTA	Male	Iranian	+	+	+	–	+	–	+	+
doi:10.1016/j.annder.2019.09.619	c.466C>T	Female	French	+	+	+	–	+	+	–	+
	c.467G<A	Female	French	+	+	+	–	+	–	–	+
doi:10.1111/jdv.14874	c.648_683del36	Male	Chinese	+	+	+	–	+	–	–	+
	c.925–2A>G	Female	Chinese	+	+	+	–	+	–	–	+
	c.916C>A	Male	Chinese	+	+	+	–	+	+	–	+
doi:10.1111/1346-8138.14606	c.511A>T	Male	Japanese	+	+	+	+	+	–	–	+
	c.5delG	Male	Japanese	+	+	+	+	+	–	–	+
	c.915_922del	Male	Japanese	+	+	+	–	+	–	–	+

Notes: +: The patient has this clinical manifestation; –: The patient had no such clinical manifestations.

Data Sharing Statement

The data analyzed in this study are available from the appropriate authors upon reasonable request.