Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome
Structural and functional properties of the fused exons. (a) Schematic representation of the rearranged genome and mRNA structures. The white and the black boxes of CYP19A1 exon 2 show untranslated region and coding region, respectively. For genome, the striped and the painted arrows indicate noncoding and coding exons, respectively (5′→3′). The inverted genomic regions are delineated in blue lines. For mRNA, colored striped boxes represent noncoding regions of each gene. The DMXL2-CYP19A1 chimeric mRNA has two translation initiation codons and therefore is destined to produce not only CYP19A1 protein but also a 47 amino acid protein which is predicted to undergo nonsense-mediated mRNA decay (NMD). The deletion and the inversion types are associated with heterozygous impairment of neighboring genes (deletion or disconnection between noncoding exon(s) and the following coding exons). The inversion subtype 1 is accompanied by inversion of eight of the 11 CYP19A1 exons 1, and the inversion subtype 2 is associated with inversion of the placenta-specific CYP19A1 exon I.1. (b) Expression patterns of CYP19A1 and the five neighboring genes involved in the chimeric gene formation . Relative mRNA levels against TBP in normal human tissues are shown.