Mutations in Genes Encoding Transcription Factors: The Nuclear Receptor Superfamily

Abstract In Chapters 5 through 14, mutations that affect the structure and/or function of specific transcription factors and result in human disease will be described. As in the previous chapter, the intent is not to catalogue all known mutations but rather to provide examples that illustrate principles of molecular pathophysiology that will be applicable to the ever expanding list of such conditions that is being reported in the molecular biology and clinical literature. In contrast to the mutations in cis-acting elements, the mutations in trans-acting factors affect the structure of the protein product of a gene. In the text, gene symbols will be indicated by italicized letters (all capitalized for human genes, first letter only for mouse genes), whereas the protein product of a gene will be indicated by unitalicized capital letters (for both human and mouse proteins). Missense mutations result in substitution of one amino acid for another and will be designated in the text using the single-letter code for amino acids (see Table 5.1). For example, the mutation C23S (due to a TGT AGT transversion) would result in substitution of serine for cysteine at residue 23 of the protein. Nonsense mutations result in premature termination of translation, which is designated by an X. Thus, the mutation C23X (due to a TGT TGA transversion) would result in translation of a truncated polypeptide containing only 22 amino acid residues.