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Objective Mutations in the EDA gene, encoding the epithelial morphogen ectodysplasin-A, can result in different but overlapping phenotypes. Therefore the aim of the study was to search for etiological variations of EDA and other candidate genes in two unrelated Egyptian male children with sporadic non-syndromic tooth agenesis (NTA) and hypohidrotic ectodermal dysplasia (HED). Design Direct sequencing of the coding regions including exon-intron boundaries of EDA, MSX1, PAX9, WNT10A and EDAR was performed in probands and their available family members. Results Two etiological mutations were found in the EDA coding region. The patient with NTA in both deciduous and permanent dentition was a carrier of a novel in-frame deletion situated in the short collagenous domain (c.663-680delTCCTCCTGGTCCTCAAGG, p.222-227delPPGPQG). The second mutation, located outside the minimal furin consensus motif (c.463C>T, p.Arg155Cys, rs132630312), was identified in the patient exhibiting all typical features of HED. The identified EDA mutations were not detected in probands’ family members as well as in 188 unrelated control individuals. No pathogenic variants were found in the MSX1, PAX9, WNT10A and EDAR genes. Conclusion Our results increase the knowledge of the spectrum of EDA mutations and confirm that this gene is an important candidate gene for two developmental diseases sharing the common feature of the congenital lack of teeth. In addition, these results can support the hypothesis that X-linked HED and EDA-related NTA are the same disease with different degrees of severity.

X-linked hypohidrotic ectodermal dysplasia (XLHED) can be characterized by hypohidrosis, sparse hair, hypodontia, and characteristic facial features and is usually caused by mutations of ectodysplasin A (EDA) gene located on the X chromosome. In this study, we examined a HED pedigree and studied the molecular genetics of the disease. A novel missense mutation was revealed by direct sequencing analysis in the EDA exon 7 (c.913 A > C, p.S305R). The impact of the mutation on the protein was studied in vitro in human embryonic kidney 293 T cells transfected with mutant or wild type forms of EDA. The mutant-type EDA1 protein showed impaired solubility comparing with wild-type EDA1. This novel missense EDA mutation was considered to be the cause of HED in the pedigree reported here. Our findings, combined with those reported elsewhere, provide an improved understanding of the pathogenic mechanism of HED as well as important information for a genetic diagnosis.

Objective To summarize the phenotypic characters of Chinese X-linked hypohidrotic ectodermal dysplasia (XLHED) subjects. Design Twelve affected and 24 carriers from seven Chinese pedigrees were recruited. The development of their hair, tooth, skin and sweat gland was (semi-)quantitatively evaluated. From 100 to 250 normal controls were used to exclude polymorphisms in each family. Results Different from the previous reports, these Chinese subjects had more symmetrical and severe oligodontia. The mean number of permanent teeth missing was 23.5, and mandibular molars were preferentially affected. Compared to the age- and gender-matching controls, the affected had evident deep and well-defined facial wrinkles especially in the forehead, periorbital and cheek. Missing anterior teeth, conical canines and slow growth of hair were the main findings of female carriers. In addition, there was no evident relationship between phenotype and genotype. Conclusions To the best of our knowledge, this was the first semi-quantitative phenotypic report of subjects of Chinese descent.