Turkish Ectodermal Dysplasia Cohort: From Phenotype to Genotype in 17 Families

Abstract

Hypohidrotic or anhidrotic ectodermal dysplasia (HED/EDA) is characterized by impaired development of the hair, teeth, or sweat glands. HED/EDA is inherited in an X-linked, autosomal dominant, or autosomal recessive pattern and caused by the pathogenic variants in 4 genes: EDA, EDAR, EDARADD, and WNT10A. The aim of the present study was to perform molecular screening of these 4 genes in a cohort of Turkish individuals diagnosed with HED/EDA. We screened for pathogenic variants of WNT10A, EDA, EDAR, and EDARADD through Sanger sequencing. We further assessed the clinical profiles of the affected individuals in order to establish phenotype-genotype correlation. In 17 (63%) out of 27 families, 17 pathogenic variants, 8 being novel, were detected in the 4 well-known ectodermal dysplasia genes. EDAR and EDA variants were identified in 6 families each, WNT10A variants in 4, and an EDARADD variant in 1, accounting for 35.3, 35.3, 23.5, and 5.9% of mutation-positive families, respectively. The low mutation detection rate of the cohort and the number of the EDAR pathogenic variants being as high as the EDA ones were the most noteworthy findings which could be attributed to the high consanguinity rate.

A novel c.916C>A EDA gene pathogenic variant in a boy with X‐linked hypohidrotic ectodermal dysplasia

“…More than half of these variants are localized to exons 1, 3 and 5. This report supports the observation that patients with EDA mutations are more likely to exhibit the characteristic XLHED triad of hypodontia, anhidrosis/hypohidrosis and hypotricosis 4,12 as opposed to patients with isolated microdontia and lack of facial dysmorphism, who are more likely to harbour WNT10A mutations 4 …”

The characterization of hypodontia, hypohidrosis, and hypotrichosis associated with X‐linked hypohidrotic ectodermal dysplasia: A systematic review

“…The weighted average of nine articles evaluating males was 83.6% with sparse hair, 11.8% with alopecia, and 88.1% with any degree of reduced hair. Cluzeau et al (2011) and Güven et al () both reported data for hypotrichosis categorically and thus could not be included in the data for males. Cluzeau et al (2011) categorized hypotrichosis by severity as no effect, mild, moderate, or severe but did not explain the criteria for these categories.…”

“…Of the 29 males, 100% had some degree of hypotrichosis: 9 had mild, 13 had moderate, and 7 had severe. Güven et al () categorized hypotrichosis using plus signs; the more plus signs the higher the severity. Of the 6 males, all had some degree of hypotrichosis as well, with 3 having one plus sign and 3 having two.…”

“…Cluzeau et al (2011) reported data for 6 females and found 100% had some degree of hypotrichosis: 2 had mild, 3 had moderate, and 1 had severe. Güven et al () reported that 3 of 6 females had mild hair anomalies but did not provide further details.…”

“…For males, seven studies reported data on abnormal crown morphology (tapered or conical crown shape). Güven et al () reported that 5 of 6 males had conical incisors and 1 male had tapered incisors. They additionally reported that 3 of 6 females had mild anomalies that were not further described.…”