CPT® Code 81260

IKBKAP (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein) (eg, familial dysautonomia) gene analysis, common variants (eg, 2507+6T>C, R696P)

Molecular genetic testing, specifically for the IKBKAP gene, is a critical procedure aimed at identifying mutations that can lead to familial dysautonomia. The IKBKAP gene provides essential instructions for the production of the IKAP protein, which is a component of a six-protein elongation complex. This complex interacts with enzymes that are vital for transcription, the process through which genetic information is transferred from DNA to the cellular machinery responsible for protein synthesis. When there are two copies of the mutated IKBKAP gene present in an individual's cells, the splicing process that creates the blueprint for the IKAP protein is disrupted. This disruption results in an inconsistent production of the IKAP protein, which is particularly detrimental to brain cells that rely on adequate levels of this protein for proper function. Familial dysautonomia is inherited in an autosomal recessive manner, meaning that an individual must inherit mutations from both parents to develop the disorder. Those who inherit the mutation from only one parent are considered carriers and typically do not exhibit symptoms. The disorder is most prevalent among individuals of Ashkenazi Jewish descent, particularly those from Central and Eastern Europe. The IKBKAP gene is located on chromosome 9, with the most common mutations being IVS20(+6TC), also represented as 2507+6T>C, which accounts for nearly 99% of cases, and R696P. Familial dysautonomia significantly impacts the autonomic nervous system, which governs involuntary bodily functions such as breathing, digestion, and heart rate, as well as the sensory nervous system, which is responsible for sensations like pain and temperature. Symptoms of this disorder typically manifest in infancy or early childhood and can include a range of serious health issues, such as difficulty maintaining body temperature, poor feeding, recurrent pneumonia, and growth retardation. The severity of the disorder can lead to a significantly reduced life expectancy, with approximately half of those affected not surviving past the age of 40. Therefore, molecular genetic testing is crucial for individuals exhibiting symptoms of familial dysautonomia or those with a family history of the condition.