The insulin-3 gene: lack of a genetic basis for human cryptorchidism.
OBJECTIVE
The etiology of cryptorchidism appears to be multifactorial and related to hormonal and mechanical factors. Recently, the insulin-3 gene (INSL3) was noted to have a role in mouse gubernacular development and testicular descent. Knockout male mice for the INSL3 gene show isolated bilateral cryptorchidism. This phenotype suggests that INSL3 may have a role in the development of human cryptorchidism. Using single strand conformational polymorphism analysis we detected mutations of the INSL3 gene in boys with cryptorchidism.


METHODS
Genomic DNA from 118 boys with cryptorchidism and 48 normal controls were obtained from 3 institutions. Using polymerase chain reaction with INSL3 sequence specific primers DNA fragments were analyzed using single strand conformational polymorphism reactions. Samples with band shifts were re-amplified and sequenced to detect mutations.


RESULTS
A single base substitution (G greater than A) causing an amino acid change (missense mutation) was identified in 27 of 118 cryptorchid (23%) samples and 12 of 48 normal (25%) samples. Two other base substitutions did not produce alterations in the amino acid sequence (silent mutations).


CONCLUSIONS
Although a common polymorphism was detected in the INSL3 gene, no specific mutations were detected in a large population of individuals with cryptorchidism. Therefore, mutations in the coding region of the INSL3 gene are not a common cause of human cryptorchidism.
Baker
Linda A
LA
John W. Duckett, M. D. Laboratory in Pediatric Urology, Department of Urology and Center for Developmental Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
Nef
Serge
S
Nguyen
Michael T
MT
Stapleton
Ronita
R
Nordenskjold
Agneta
A
Pohl
Hans
H
Parada
Luis F
LF
D002648:Child; D003456:Cryptorchidism / Q000235:genetics*; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007328:Insulin; D008297:Male; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D020539:Sequence Analysis, Protein
D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins