The Fordham Laboratory for Familial Dysautonomia Research is the first group in the world to submit an article demonstrating that FD is caused by mutations in the IKBKAP (now known as ELP1) gene. This gene codes for the production of a protein known as IKAP (now known as ELP1). The most prevalent (“major”) mutation, which is found in more than 99% of the individuals with FD, causes the RNA encoded by the IKBKAP (now known as ELP1) gene to be processed incorrectly. This incorrectly made RNA generates a defective, non-functional, IKAP (now known as ELP1). The insufficient production of functional IKAP (now known as ELP1) results in the clinical manifestations of FD.



Individuals of Ashkenazi Jewish (AJ) descent can have within their genetic information mutations that, when transmitted from both mother and father, cause such diseases as Tay Sachs, Canavan Disease and Fanconi Anemia. In 1949, the physicians Conrad Riley and Richard Day reported the presence of a genetic disease in the AJ population that causes severe autonomic dysfunction. This disorder, which was originally known as Riley-Day syndrome, is now referred to as Familial Dysautonomia (FD). Despite significant research efforts, the mutation responsible for FD eluded identification. Genetic screening tests, which were available for many genetic diseases present in the AJ population, were not available for FD, as the disease-causing mutation had not been identified. Without such a test, many children were born with this very serious disorder. Frustrated by the lack of progress, the research team at Fordham University set aside their ongoing research program in immunology and cancer and focused their research efforts on the identification of the FD-causing mutation. Working together with a hard-working and determined group of students, Dr. Sylvia Anderson and Dr. Berish Rubin identified the FD-causing mutations within three months of commencing this research effort.



The discovery made by the Fordham researchers enabled the development of genetic screening programs that have greatly reduced the number of children born with FD. The discovery of the FD-causing mutation was viewed by the scientific and medical community as a significant breakthrough, as it provided effective genetic screening for a disease-causing mutation that is as prevalent in the AJ population as the Tay Sachs-causing mutations. The importance of this finding was further highlighted by the decision of the Committee on Genetics of the American College of Obstetrics and Gynecology to recommend that couples of AJ descent be provided carrier screening for FD.



Prior to the identification of the genetic cause of FD, the therapies available for individuals with FD exclusively targeted the symptoms associated with this disorder but did not address the underlying genetic defect. The identification of the FD-causing mutation has allowed researchers to develop treatments that effectively address and reverse the genetic deficit caused by this mutation and thereby alter the course of this disease. A new era had dawned!

Gene Discovery Publications:
Familial dysautonomia is caused by mutations of the IKAP gene (PDF)
Genomic organization and chromosomal localization of the mouse IKBKAP gene (PDF)