change in amino acids (the building blocks of proteins). In these cases, arginine is replaced by proline at position 696 in the IKAP protein's chain of amino acids (also written as Arg696Pro), or proline is replaced by leucine at position 914 (also written as Pro914Leu). Together, these mutations cause the resulting IKAP protein to malfunction. As an autosomal recessive disorder, two mutated alleles of the IKBKAP gene are required for the disorder to manifest. However, despite the predominance of the same single-base mutation being the reputed cause of familial dysautonomia, the severity of the affected phenotype varies within and between families. Kinetin (6-furfurylaminopurine) has been found to have the capacity to repair the splicing defect and increase wild-type IKBKAP mRNA expression in vivo. Further research is still required to assess the fitness of kinetin as a possible future oral treatment. Model organisms Model organisms have been used in the study of IKBKAP gene function. Mouse A conditional knockout mouse line, called Ikbkaptm1a(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out and two phenotypes were reported. No homozygous mutant embryos were identified during gestation, and in a separate study, none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no significant abnormalities were observed in these animals. Saccharomyces cerevisiae The homologous protein for IKAP in yeast is Elp1, with 29% identity and 46% similarity detected between the proteins. The yeast Elp1 protein is a subunit of a three-protein RNA polymerase II-associated elongator complex. Drosophila melanogaster The IKBKAP gene homolog in fruit flies is the CG10535 gene, encoding the D-elp1 protein — the largest of three subunits making the RNA polymerase II core elongator complex. This subunit was found to have RNA-dependent RNA polymerase activity, through which it could synthesize double-stranded RNA from single-stranded RNA templates. See also Familial dysautonomia References Further reading Full text External links GeneReviews/NCBI/NIH/UW entry on Familial Dysautonomia Genes mutated in mice EC 2.7.11