Hypohidrotic ectodermal dysplasia caused by an intragenic duplication in EDAR

Lise Graversen; Mette Sommerlund; Casper Kruse; Hans Gjørup; Pernille Axel Gregersen; Uffe Birk Jensen; Jenny Blechingberg

doi:10.1016/j.ejmg.2024.104982

Hypohidrotic ectodermal dysplasia caused by an intragenic duplication in EDAR

Eur J Med Genet. 2024 Oct 29:72:104982. doi: 10.1016/j.ejmg.2024.104982. Online ahead of print.

Authors

Lise Graversen¹, Mette Sommerlund², Casper Kruse³, Hans Gjørup³, Pernille Axel Gregersen⁴, Uffe Birk Jensen⁵, Jenny Blechingberg⁶

Affiliations

¹ Department of Clinical Genetics, Aarhus University Hospital, Olof Palmes Allé 49, 8200 Aarhus N, Denmark. Electronic address: lisega@rm.dk.
² Department of Dermatology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 67, 8200 Aarhus N, Denmark.
³ Center for Oral Health in Rare Diseases, Department of Maxillofacial Surgery, Aarhus University Hospital, Aarhus, Denmark.
⁴ Department of Clinical Genetics, Aarhus University Hospital, Olof Palmes Allé 49, 8200 Aarhus N, Denmark; Center for Rare Diseases, Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Health, Aarhus University, Aarhus, Denmark.
⁵ Department of Clinical Genetics, Aarhus University Hospital, Olof Palmes Allé 49, 8200 Aarhus N, Denmark; Department of Clinical Medicine, Health, Aarhus University, Aarhus, Denmark.
⁶ Department of Clinical Genetics, Aarhus University Hospital, Olof Palmes Allé 49, 8200 Aarhus N, Denmark.

PMID: 39476951
DOI: 10.1016/j.ejmg.2024.104982

Abstract

Hypohidrotic Ectodermal Dysplasia is a syndrome with hypotrichosis, hypohidrosis, and hypodontia as the main symptoms. The prevalence is estimated to one in 5000-10,000 persons. In 10-15% the disease is caused by pathogenic variants in EDAR, and most of the known causal variants to date are missense or nonsense variants. We present a patient with classic Hypohidrotic Ectodermal Dysplasia and mammary gland aplasia with a duplication within EDAR as the likely cause. The duplication is de novo in the patient, and genome sequencing of DNA extracted from blood has revealed that the duplication is in tandem conformation, most likely entailing an altered EDAR protein with a dominant negative effect. This is to our knowledge the first report of an intragenic duplication in EDAR as causal for Hypohidrotic Ectodermal Dysplasia.

Keywords: Ectodermal dysplasia; Edar receptor; Genetic diseases; Inborn; Rare diseases.

Publication types

Case Reports