Gonadotropin-independent precocious puberty associated with a somatic activating mutation of the LH receptor gene: detection of a mutation present in only a small fraction of cells from testicular tissue using wild-type blocking polymerase chain reaction and laser-capture microdissection

Objective Leydig cells are the principal source of testosterone, and boys with Leydig cell tumors typically have signs of gonadotropin-independent precocious puberty as a result of testosterone secretion by the tumor. A single somatic activating mutation of the LH receptor gene, Asp578His, limited to the tumoral Leydig cells, has been described in a few boys with gonadotropin-independent precocious puberty. We report a molecular study of a boy with gonadotropin-independent precocious puberty caused by a Leydig cell tumor. Design and setting This is a clinical case report from the Kobe Children’s Hospital. Patient and methods One patient with gonadotropin-independent precocious puberty caused by a Leydig cell tumor underwent a left orchidectomy. We performed a genetic study of the tumoral Leydig cells. Result Using wild-type blocking PCR (WTB-PCR) and laser-capture microdissection (LCM), we found that the Asp578His mutation of the LH receptor gene was exclusively localized to the tumoral Leydig cells and was absent in the adjacent normal tissue and leukocytes. Conclusions WTB-PCR and LCM are powerful techniques that can detect a somatic mutation present in only a small fraction of cells from heterozygous tissue samples.