Aromatase excess syndrome in a family with upstream deletion of CYP19A1
Aromatase excess syndrome in a family with upstream deletion of CYP19A1
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CYP19A1上游缺失家族的芳香酶过量综合征
DOI：
10.1111/cen.12329
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Fukami M*
中科院分区：
文献类型：
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作者：
Shihara D;Miyado M;Nakabayashi K;Shozu M;Nagasaki K;Ogata T;Fukami M*
芳香化酶过量综合征（AEXS）是由CYP 19 A1在15 q21处过度表达引起的常染色体显性遗传疾病。1 AEXS的突出临床特征是由雌激素过量引起的男性乳房发育和骨龄提前。1-3到目前为止，已在9个家系的23例患者中发现了6个15 q21的基因组重排。1-3这些重排包括涉及CYP 19 A1的启动子区域的重复，以及产生由CYP 19 A1的编码外显子和相邻基因的启动子相关外显子组成的嵌合基因的缺失和倒位。由于报告的患者数量较少，进一步的研究是必要的，以澄清分子基础和表型的AEXS.Here，我们确定了一个日本家庭与AEXS 15 q2142和迄今未报告的缺失。这项研究得到了国家儿童健康与发展中心机构审查委员会的批准。先证者是一名12岁男孩，确诊为男性乳房发育症。体格检查显示与年龄相适应的性发育（图1和表S1）。他的哥哥和父亲也表现出男性乳房发育。14岁的妹妹经历了初潮。母亲临床表现正常。先证者和兄弟的骨龄显著提前。对生长记录的评估显示，先证者和兄弟在6-7岁时生长速度达到峰值，而姐妹在4-6岁时显示出高生长速度（图1）。父亲的血雌二醇（E2）值略微升高，先证者和兄弟的血雌二醇（E2）值仍无法检测到（表S1）。
Aromatase excess syndrome (AEXS) is an autosomal dominant disorder caused by overexpression of CYP19A1 at 15q21. 1 Salient clinical features of AEXS are gynaecomastia and advanced bone age resulting from oestrogen excess. 1–3 To date, six genomic rearrangements at 15q21 have been identified in 23 patients from nine families. 1–3 These rearrangements include duplications involving the promoter region of CYP19A1, and deletions and inversions that create chimeric genes consisting of coding exons of CYP19A1 and promoter-associated exons of neighbouring genes. Given the small number of reported patients, further studies are necessary to clarify molecular basis and phenotypes of AEXS.Here, we identified a Japanese family with AEXS and hitherto unreported deletion at 15q2142. This study was approved by the Institutional Review Board Committees at the National Center for Child Health and Development. The proband was a 12-yearold boy ascertained by gynaecomastia. Physical examination revealed age-appropriate sexual development (Fig. 1 and Table S1). His brother and father also exhibited gynaecomastia. The 14-year-old sister experienced early menarche. The mother was clinically normal. Bone age was significantly advanced in the proband and brother. Assessment of growth records revealed that the proband and brother had a peak growth velocity at 6–7 years of age, and the sister showed a high growth velocity at 4–6 years of age (Fig. 1). Blood oestradiol (E2) values were slightly elevated in the father and remained undetectable in the proband and brother (Table S1).