Novel Edaradd Variant in Ectodermal Dysplasia Unveiled by Whole-Exome Sequencing Publisher



Kalayinia S¹ ; Seyed Aliakbar S² ; Soheili A² ; Rabbani A³ ; Masoumi T¹ ; Hosseinkhani Z^{1, 5} ; Mirab Samiee S¹ ; Mahdieh N^{1, 4, 6} Show Affiliations
Source: Biochemical Genetics Published:2025

Abstract

Ectodermal dysplasia (ED) represents a group of genetic disorders affecting the development of ectodermal-derived structures, including teeth, hair, nails, and sweat glands. Ectodermal dysplasia (HED), the most common form, is frequently associated with severe dental anomalies such as hypodontia and aberrant tooth morphology, profoundly affecting oral health and quality of life. We present an Iranian patient due to a novel pathogenic variant in the EDARADD gene. A 20-month-old female presenting with clinical features suggestive of ectodermal dysplasia, including significant dental abnormalities, was evaluated at the Rajaie Cardiovascular Medical and Research Center. Genomic DNA was extracted from peripheral blood, and WES was performed to identify potential pathogenic variants. Variant filtering, annotation, and pathogenicity assessment were conducted using standard databases, in silico tools, and the American College of Medical Genetics and Genomics (ACMG) guidelines. Segregation analysis was performed to confirm the inheritance pattern. WES revealed a novel frameshift variant, c.36dupT, in the EDARADD gene, predicted to result in a loss of protein function. The variant was classified as pathogenic according to ACMG criteria and correlated with the patient’s clinical presentation, including hypodontia, sparse hair, and onychodystrophy. Segregation analysis confirmed an autosomal recessive inheritance pattern, with both parents identified as heterozygous carriers. The dental phenotype, particularly the severe hypodontia, was a hallmark feature aligning with the genetic findings. Identifying the novel c.36dupT variant in EDARADD provides important insights into the genetic basis of ectodermal dysplasia. The study underscores the significance of integrating clinical data with advanced genetic testing, such as WES, for accurate diagnosis and personalized treatment of patients with rare genetic disorders. Further studies with larger cohorts are necessary to understand the broader implications of EDARADD mutations in ectodermal dysplasia and their potential role in clinical diagnostics. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.