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International Journal of Endocrinology
Volume 2012 (2012), Article ID 584807, 8 pages
http://dx.doi.org/10.1155/2012/584807
Review Article

Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome

1Department of Molecular Endocrinology, National Research Institute for Child Health and Development, 2-10-1 Ohkura, Setagaya, Tokyo 157-8535, Japan
2Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City 206-8670, Japan
3Department of Pediatrics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Shizuoka, Hamamatsu 431-3192, Japan

Received 9 July 2011; Revised 22 September 2011; Accepted 2 October 2011

Academic Editor: Rodolfo Rey

Copyright © 2012 Maki Fukami et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Aromatase excess syndrome (AEXS) is a rare autosomal dominant disorder characterized by gynecomastia. This condition is caused by overexpression of CYP19A1 encoding aromatase, and three types of cryptic genomic rearrangement around CYP19A1, that is, duplications, deletions, and inversions, have been identified in AEXS. Duplications appear to have caused CYP19A1 overexpression because of an increased number of physiological promoters, whereas deletions and inversions would have induced wide CYP19A1 expression due to the formation of chimeric genes consisting of a noncoding exon(s) of a neighboring gene and CYP19A1 coding exons. Genotype-phenotype analysis implies that phenotypic severity of AEXS is primarily determined by the expression pattern of CYP19A1 and the chimeric genes and by the structural property of the fused exons with a promoter function (i.e., the presence or the absence of a natural translation start codon). These results provide novel information about molecular mechanisms of human genetic disorders and biological function of estrogens.