• PMID: 19017913
• Gene Name: INSL3
• Condition: Infertility
• Association: Two patients had a INSL3 gene mutation
• PMID: 19017913
• Gene Name: INSL3
• Condition: Cryptorchidism
• Association: In a small percentage of the study population, there was a statistically significant association between bilateral and persistentcryptorchidism and genetic alterations, including Klinefelter syndrome and INSL3 receptor gene mutations.
• Population size: 900
• Population details: 900 (600 male infants with cryptorchidism, 300 noncryptorchid male children as controls)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Cryptorchidism

Genetic alterations associated with cryptorchidism

Ferlin A, Zuccarello D, Zuccarello B, Chirico MR, Zanon GF, Foresta C.

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. FAU - Ferlin, Alberto AU - Ferlin A AD - Section of Clinical Pathology and Centre for Male Gamete Cryopreservation, Department of Histology, Microbiology and Medical Biotechnologies, University of Padova, Via Gabelli 63, 35121 Padova, Italy. FAU - Zuccarello, Daniela AU - Zuccarello D FAU - Zuccarello, Biagio AU - Zuccarello B FAU - Chirico, Maria Rosaria AU - Chirico MR FAU - Zanon, Giovanni Franco AU - Zanon GF