A single somatic activating Asp578His mutation of the luteinizing hormone receptor causes Leydig cell tumour in boys with gonadotropin‐independent precocious puberty

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

“…This single somatic Asp578His mutation of the LH receptor gene has been described in nine boys, including our case, with gonadotropin-independent precocious puberty caused by Leydig cell tumors [5][6][7][8][9]. In contrast, more than 15 germline mutations causing familial male-limited gonadotropin-independent precocious puberty have been reported [12].…”

“…Leydig cells are the principal source of testosterone, and boys with Leydig cell tumors typically have signs of gonadotropinindependent precocious puberty as a result of testosterone secretion by the tumor. A single somatic activating mutation of the LH receptor gene, Asp578His, limited to tumor cells, has been described in a few boys with gonadotropin-independent precocious puberty [5][6][7][8][9]. Here, we describe a molecular study of a boy with gonadotropin-independent precocious puberty caused by a Leydig cell tumor.…”

Testicular and paratesticular tumors and tumor-like lesions in the first 2 decades

“…161,162 Some Leydig cell tumors in children have activating mutations of the luteinizing hormone receptor that are absent in the non-neoplastic tissues. [163][164][165] These acquired mutations occur at codon 578 of exon 11, leading to replacement of aspartic acid by histidine, and cause constitutive activation of the receptor. Such activation, in turn, is felt to cause Leydig cell proliferation, followed by tumor formation and neoplastic androgen production.…”

Sexual Pseudo-Precocity Caused by a Somatic Activating Mutation of the LH Receptor Preceding True Sexual Precocity

“…Not only is this activating mutation of the LH receptor gene present in Leydig cell tumors, but it can also be found in nodular Leydig cell hyperplasia [24]. We detected the same mutation in our patient and till now this mutation exclusively determines the sporadic Leydig cell tumor caused by a somatic activating mutation of the LH receptor gene [25]. One year after orchiectomy with normalization of plasma testosterone, our patient presented with gonadotropin-dependent precocious puberty.…”