Deafness, Autosomal Dominant 4B (DFNA4B) via the CEACAM16 Gene

Nonsyndromic hearing loss is characterized by difficulty or inability to hear that is not associated with any visible defects involving the external ear, other organs, or any other medical condition. Nonsyndromic hearing loss may be associated with abnormalities involving the middle ear and/or the inner ear (Ciuman 2013; Dodson et al. 2011; Hilgert et al. 2009). At least 70% of cases involving hearing loss are nonsyndromic (Van Camp et al. 1997).

Nonsyndromic hearing loss and deafness due to pathogenic variants in the CEACAM16 gene is associated with postlingual, bilateral, moderate to profound, progressive sensorineural hearing impairment. Onset of hearing loss is typically in the first or second decade affecting high frequencies and progressing to profound hearing loss affecting all frequencies. No visual, vestibular or temporal bone abnormalities are present (Zheng et al. 2011; Wang et al. 2015; Hofrichter et al. 2015).

DFNA4B is an autosomal dominant hearing disorder that is caused by pathogenic sequence variants in the carcinoembryonic antigen related cell adhesion molecule 16 (CEACAM16) gene, which is located on chromosome 19q13.31-q13.32. The CEACAM16 gene spans 15.6 kb and consists of 6 coding exons that produce a 425 amino acid protein that is a component of the CEACAM family of adhesion proteins. In the mouse inner ear the CEACAM16 gene is expressed in the outer hair cells and the CEACAM16 protein localizes to the tips of the stereocilia in outer hair cells as well as the tectorial membrane (Zheng et al. 2011).

Only three missense variants in CEACAM16 have to date been reported as pathogenic for hearing loss in three different families of American, Chinese and German origin (Zheng et al. 2011; Wang et al. 2015; Hofrichter et al. 2015).

The clinical sensitivity of this sequencing test is difficult to predict because only three missense variants in CEACAM16 have been reported as pathogenic for hearing loss in three different families of American, Chinese and German origin (Zheng et al. 2011; Wang et al. 2015; Hofrichter et al. 2015). Analytical sensitivity should be high because all reported variants are detectable by sequencing.

No deletion or duplication variants associated with CEACAM16 have been reported as pathogenic for hearing loss.

This test provides full coverage of all coding exons of the CEACAM16 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).