• PMID: 15533513
• Gene Name: INSL3
• Condition: Infertility
• Association: Polymorphic alleles of INSL3 and GREAT were found in the study population, but no deleterious mutations were observed among individuals with familial cryptorchidism.
• PMID: 15533513
• Gene Name: INSL3
• Condition: Familial cryptorchidism
• Association: The study found polymorphic alleles of INSL3 and GREAT, but no deleterious mutations among individuals with familial cryptorchidism. Thus, mutations in these two genes are responsible only for a small proportion of familial cryptorchidism.
• Mutation: One missense (A60T) substitution in exon 1 of INSL3 and two silent substitutions in exon 12 and one missense (I604V) substitution in exon 17 of GREAT
• Population size: 13
• Population details: 13 individuals with personal and family histories of cryptorchidism
• Sex: Male
• Infertility type: Male infertiltiy
• Associated genes: INSL3, LGR8/GREAT
• Other associated phenotypes: Familial cryptorchidism

Mutation analysis of INSL3 and GREAT/LGR8 genes in familial cryptorchidism

Feng S, Cortessis VK, Hwang A, Hardy B, Koh CJ, Bogatcheva NV, Agoulnik AI.

OBJECTIVES: Male mice deficient in insulin-like 3 hormone (Insl3) or its receptor, Great/Lgr8, exhibit cryptorchidism. Recently, sequence analysis of the human INSL3 and GREAT genes identified several allelic variants. These include polymorphisms without apparent functional consequence and a few alleles encoding products with compromised function. However, loss-of-function alleles appear to be rare in human cryptorchidism. Most patients studied to date are presumed to have had sporadic cryptorchidism. We postulated that any genotypic variants predisposing to cryptorchidism would be more prevalent among patients with familial cryptorchidism. METHODS: We isolated genomic DNA from 13 individuals with personal and family histories of cryptorchidism and used polymerase chain reaction to amplify all exons of both INSL3 and GREAT, as well as INSL3 proximal promoter sequence, including a putative SF-1 transcription factor binding site. We directly sequenced all 20 amplicons and compared them with the wild-type alleles. RESULTS: We detected two silent substitutions and one missense (A60T) substitution in exon 1 of INSL3 and two silent substitutions in exon 12 and one missense (I604V) substitution in exon 17 of GREAT, all previously described. We found that in vitro the I604V GREAT variant receptor responds to INSL3 stimulation similarly to the wild-type receptor. CONCLUSIONS: We found polymorphic alleles of INSL3 and GREAT, but no deleterious mutations among individuals with familial cryptorchidism. Thus, mutations in these two genes are responsible only for a small proportion of familial cryptorchidism. FAU - Feng, Shu AU - Feng S AD - Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA. FAU - Cortessis, Victoria K AU - Cortessis VK FAU - Hwang, Andrew AU - Hwang A FAU - Hardy, Brian AU - Hardy B FAU - Koh, Chester J AU - Koh CJ FAU - Bogatcheva, Natalia V AU - Bogatcheva NV