Ectodermal Dysplasia via the EDARADD Gene

Ectodermal dysplasia (ED) is a clinically and genetically heterogeneous disorder characterized by abnormal development of hair, teeth, nail or sweat glands (Visinoni et al. 2009). ED can be clinically divided into more than 150 subtypes. Hypohidrotic ectodermal dysplasia (HED) is characterized by hypodontia, hypohidrosis and hypotrichosis. The major clinical signs are thin and dry scalp hair, eyelashes and eyebrows, reduced ability to sweat, and congenital missing or abnormal formed teeth. Some patients may have abnormal craniofacial features such as prominent forehead, saddle-back nose, and protruding lips (Visinoni et al. 2009; Wright et al. 2014). HED is currently known to be caused by mutations in the EDA, EDAR, EDARADD and WNT10A genes (Cluzeau et al. 2011).

Mutations in the EDARADD gene cause autosomal dominant and recessive forms of the ectodermal dysplasia and tooth agenesis. The EDARADD protein serves as a component in the EDA-EDAR-EDARADD and the NF-kappa-B pathways, which play a key role in the development of ectodermal structures such as hair follicles, sweat glands, and teeth. To date, about 10 unique pathogenic variants have been reported. They are: 6 missense and 2 small deletion and insertion (Cluzeau et al. 2011 and Human Gene Mutation Database).

Mutations in EDARADD account for 1-2% of pathogenic mutations identified in HED patients (Wright et al. 2014). In another study, EDARADD mutations were found in 1 out of 61 HED/EDA patients (Cluzeau et al. 2011).

No large deletions or duplications involving EDARADD have been reported to date (Human Gene Mutation Database).

This test provides full coverage of all coding exons of the EDARADD gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).