Showing papers by "Francis X. Schneck published in 2000"

Insulin-like 3/relaxin-like factor gene mutations are associated with cryptorchidism.

Abstract: Cryptorchidism is a common anomaly of male sexual differentia- tion. Two phases of testicular descent are recognized, transabdominal and inguinoscrotal. With evidence that androgens and Mullerian in- hibitory hormone were not completely responsible for testicular de- scent, the existence of a third testicular hormone mediating testicular descent was postulated. Insulin-like 3 (INSL3) (also known as relaxin- like factor (RLF) and Leydig insulin-like protein (LEY I-L)) is a mem- ber of the insulin/relaxin hormone superfamily that is highly ex- pressed in Leydig cells. The phenotype of transgenic mice with targeted deletion of the Insl3 gene was bilateral cryptorchidism with morphological evidence of abnormal gubernacular development. With this implicit evidence that Insl3 mediates testicular descent in mice, we performed mutation detection analysis of the coding regions of the 2 exon INSL3 gene in genomic DNA samples obtained from 145 formerly cryptorchid patients and 36 adult male controls. Single- strand conformational polymorphism analysis was used for the mu- tation detection studies. Two mutations, R49X and P69L, and several polymorphisms were identified. Both mutations were located in the connecting peptide region of the protein. The frequency of INSL3/ RLF gene mutations as a cause of cryptorchidism is low, because only 2 of 145 (1.4%) formerly cryptorchid patients were found to have mutations. (J Clin Endocrinol Metab 85: 4013- 4018, 2000)