Ectodermal Dysplasia via the WNT10A 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 pathogenic variants in the EDA, EDAR, EDARADD and WNT10A genes (Cluzeau et al. 2011).

Pathogenic variants in WNT10A cause at least three types of ectodermal dysplasia: autosomal recessive Odontoonychodermal dysplasia, autosomal recessive Schopf-Schulz-Passarge syndrome, and autosomal dominant Tooth agenesis, selective type 4. The WNT10A protein is a secreted signaling protein and serves as a ligand for members of the frizzled family of seven transmembrane receptors which play key roles in regulation of cell fate and patterning during embryogenesis. To date, more than 60 unique pathogenic variants have been reported. They are: missense (75%), small deletion and insertion (9%), nonsense (14%), one splicing and one large deletion (Cluzeau et al. 2011; Iglesias et al. 2014; and Human Gene Mutation Database).

Pathogenic variants in WNT10A are responsible for ~16% of clinically diagnosed HED patients (Cluzeau et al. 2011).

Only one gross deletion was reported in one patient affected with congenital ichthyosis, developmental delay, and periventricular white matter changes (Iglesias et al. 2014; Human Gene Mutation Database).

This test provides full coverage of all coding exons of the WNT10A 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).