Genetic Alterations Associated With Cryptorchidism
Genetic Alterations Associated With Cryptorchidism
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DOI：
10.1001/jama.2008.668
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发表时间：
2008-11-19
影响因子：
120.7
通讯作者：
Foresta, Carlo
中科院分区：
文献类型：
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作者：
Ferlin, Alberto;Zuccarello, Daniela;Foresta, Carlo
隐睾是男性儿童最常见的先天性出生缺陷，是不育和睾丸癌的重要危险因素。睾丸下降的主要调节因子是激素胰岛素样因子3（INSL 3）和睾酮，这些途径的破坏可能导致隐睾症。目的确定隐睾症的遗传变异频率。设计和设置病例对照研究，于2003年1月至2005年3月在意大利的2个儿科进行。男孩随访2 - 3年（至2008年1月），对持续性隐睾的男孩进行了隐睾固定术。我们分析了300名1 ~ 4岁的非隐睾男性儿童作为对照。主要结果测量核型异常和INSL 3、INSL 3受体和雄激素受体基因突变。（17/ 600 [ 2.8%; 95%置信区间{CI}，1.7%- 4.5%]），持续性隐睾症患者中显著更高（16/ 303 [ 5.3%; 95%CI，3.0%- 8.4%]; P=. 001)双侧隐睾组（10/ 120 [ 8.3%; 95%CI，4.1%- 14.8%]; P=. 001)与对照组相比（1/ 300 [ 0.3%; 95% CI，0.1%-0.8%]）。患有持续隐睾症的男孩发生遗传改变的几率高17倍（比值比，16.7; 95%CI，2.2- 126.5）。隐睾患者最常见的遗传学发现是8例Klinefelter综合征和5例INSL 3受体基因突变。遗传改变没有发现在男孩与低出生体重或低胎龄，谁经常自发下降的testes.Conclusion在一小部分的研究人群中，有统计学意义的双边和持续隐睾症和遗传改变，包括Klinefelter综合征和INSL 3受体基因突变之间的关联。
Context Cryptorchidism is the most frequent congenital birth defect in male children and represents an important risk factor for infertility and testicular cancer. Major regulators of testicular descent are the hormones insulin- like factor 3 ( INSL3) and testosterone, and disruption of these pathways might cause cryptorchidism.Objective To determine the frequency of genetic alterations in cryptorchidism.Design and Setting Case- control study in 2 departments of pediatric surgery in Italy between January 2003 and March 2005.Patients Six hundred male infants with cryptorchidism. Boys were followed up for 2 to 3 years ( through January 2008) and orchidopexy was performed in those who were persistently cryptorchid. We analyzed 300 noncryptorchid male children aged 1 to 4 years as controls.Main Outcome Measures Karyotype anomalies and INSL3, INSL3 receptor, and androgen receptor gene mutations.Results The frequency of genetic alterations in boys with cryptorchidism was low ( 17/ 600 [ 2.8%; 95% confidence interval {CI}, 1.7%- 4.5%]) and was significantly higher in participants with persistent cryptorchidism ( 16/ 303 [ 5.3%; 95% CI, 3.0%- 8.4%]; P=. 001) and those with bilateral cryptorchidism ( 10/ 120 [ 8.3%; 95% CI, 4.1%- 14.8%]; P=. 001) than in controls ( 1/ 300 [ 0.3%; 95% CI, 0.1%-0.8%]). Boys with persistent cryptorchidism had a 17- fold greater odds of having a genetic alteration ( odds ratio, 16.7; 95% CI, 2.2- 126.5). The most common genetic findings in those with cryptorchidism were 8 cases of Klinefelter syndrome and 5 cases of mutations in the INSL3 receptor gene. Genetic alterations were not found in boys with low birth weight or low gestational age, who had frequent spontaneous descent of the testes.Conclusion In a small percentage of the study population, there was a statistically significant association between bilateral and persistent cryptorchidism and genetic alterations, including Klinefelter syndrome and INSL3 receptor gene mutations.