CPT® Code 81253

GJB2 (gap junction protein, beta 2, 26kDa, connexin 26) (eg, nonsyndromic hearing loss) gene analysis; known familial variants

The CPT® Code 81253 pertains to the molecular genetic testing of the GJB2 gene, which encodes the gap junction protein beta 2, also known as connexin 26. This gene analysis is specifically aimed at identifying known familial variants associated with nonsyndromic hearing loss (NSHL). The GJB2 gene plays a critical role in the formation of gap junctions, which are essential for cellular communication, allowing the transport of nutrients, ions, and signaling molecules between adjacent cells. Connexin 26, the protein produced by the GJB2 gene, is particularly important in the inner ear (cochlea) and the epidermis. Located on chromosome 13, the GJB2 gene has been linked to at least 90 identified mutations that can lead to a form of deafness known as NFNB1, which is inherited in an autosomal recessive manner. In this inheritance pattern, an individual who inherits one mutated copy of the gene becomes a carrier, while inheriting two mutated copies results in the manifestation of the condition. The mutations in the GJB2 gene typically disrupt the process by which sound waves are converted into nerve impulses, leading to hearing loss. Testing for known familial variants, such as 35delG or 30delG, is particularly relevant as these deletions occur between positions 30 and 35 of the gene and are most frequently observed in Caucasian populations. In contrast, Asian populations often exhibit a deletion at position 235 (235delC), while Ashkenazi Jewish populations are more likely to have a deletion at position 167 (167delT). All these mutations result in the production of an abnormally small protein that fails to effectively bridge the functional gap between cells. Additionally, some mutations may lead to the replacement of amino acids, resulting in unstable or dysfunctional proteins that cannot form proper gap junctions. Another form of hearing loss, DFNA3, is inherited in an autosomal dominant manner, where the presence of just one mutated gene is sufficient to cause the disease.