A limited repertoire of mutations of the luteinizing hormone (LH) receptorgene in familial and sporadic patients with male LH-independent precociouspuberty

Herein, we report mutation analysis of the LH receptor gene in 17 males wit h LH-independent precocious puberty, of which 8 were familial and 9 had a n egative family history. A total of 7 different mutations tall previously re ported) were detected in 12 patients. Among 10 European familial male-limit ed precocious puberty (FMPP) patients who had a LH receptor gene mutation, none had the Asp(578)Gly mutation, which is responsible for the vast majori ty of cases in the U.S. The restricted number of activating mutations of th e LH receptor observed in this and other studies of FMPP strongly suggests that an activating phenotype is associated with very specific sites in the receptor protein. Clinical follow-up of the 5 patients who did not have LH receptor mutations shows that such cases most likely do not have true FMPP. LH receptor mutation analysis provides a sensitive tool for distinguishing true FMPP from other causes of early-onset LH-independent puberty in males .