Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome
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...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2012/584807 |
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| author | Maki Fukami Makio Shozu Tsutomu Ogata |
| author_facet | Maki Fukami Makio Shozu Tsutomu Ogata |
| author_sort | Maki Fukami |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-833620326cca4dbf98cbf55df9c7c7b1 |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-833620326cca4dbf98cbf55df9c7c7b12025-08-20T03:37:37ZengWileyInternational Journal of Endocrinology1687-83371687-83452012-01-01201210.1155/2012/584807584807Molecular Bases and Phenotypic Determinants of Aromatase Excess SyndromeMaki Fukami0Makio Shozu1Tsutomu Ogata2Department of Molecular Endocrinology, National Research Institute for Child Health and Development, 2-10-1 Ohkura, Setagaya, Tokyo 157-8535, JapanDepartment of Reproductive Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City 206-8670, JapanDepartment of Molecular Endocrinology, National Research Institute for Child Health and Development, 2-10-1 Ohkura, Setagaya, Tokyo 157-8535, JapanAromatase 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.http://dx.doi.org/10.1155/2012/584807 |
| spellingShingle | Maki Fukami Makio Shozu Tsutomu Ogata Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome International Journal of Endocrinology |
| title | Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome |
| title_full | Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome |
| title_fullStr | Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome |
| title_full_unstemmed | Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome |
| title_short | Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome |
| title_sort | molecular bases and phenotypic determinants of aromatase excess syndrome |
| url | http://dx.doi.org/10.1155/2012/584807 |
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