R171H missense mutation of INSL6 in a patient with spermatogenic failure

Insulin-like peptide 6 (INSL6) is a newly identified insulin/relaxin family peptide hormone that is predominantly expressed by the male germ cells in testes. A recent murine study demonstrated that INSL6-knockout results in spermatogenic failure. In the present study, human INSL6 gene was screened for mutations that may contribute to human spermatogenic failure. Of 249 patients and 249 healthy control subjects, a heterozygous R171H missense mutation was found in one patient. The R171H mutation probably disturbed the in vivo processing of the INSL6 prohormone because it was located at the absolutely conserved tetrabasic cleavage site between the C-peptide and the A-chain, therefore the R171H missense mutation might be responsible for human spermatogenic failure.