Sexual pseudo-precocity caused by a somatic activating mutation of the LH receptor preceding true sexual precocity.
OBJECTIVE
We describe the clinical features of a 6-year-old boy with sexual precocity caused by a somatic activating mutation of the luteinizing hormone (LH) receptor gene preceding gonadotropin-releasing hormone (GnRH)-dependent sexual precocity.


METHODS
Genomic DNA was extracted from the right testis and from the peripheral leukocytes followed by DNA amplification and sequencing of the LH receptor gene. We described the clinical characteristics including anthropometric parameters, bone age, and endocrine evaluation when the boy presented with sexual precocity. These data were compared with the clinical and hormonal evaluation after orchiectomy preceding GnRH-dependent sexual precocity and after subsequent treatment with GnRH agonist.


RESULTS
No mutation was found in the sequence of the LH receptor gene extracted from peripheral leukocytes. Interestingly, sequencing of the tumor LH receptor gene revealed a heterozygous mutation in exon 11 encoding a replacement of Asp(578)His. Despite normalization of plasma testosterone, true precocious puberty was triggered within a year.


CONCLUSIONS
Inmales with GnRH-independent sexual precocity the presence of small testicular Leydig cell tumorous lesions harboring a somatic mutation of the LH receptor gene should be considered. A close follow-up of affected patients should be instigated in order to monitor recurrence or subsequent true precocity.
Kiepe
Daniela
D
Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, Heidelberg, Germany. daniela.kiepe@med.uni-heidelberg.de
Richter-Unruh
Annette
A
Autschbach
Frank
F
Kessler
Markus
M
Schenk
Jens Peter
JP
Bettendorf
Markus
M
D019943:Amino Acid Substitution; D002648:Child; D005091:Exons / Q000235:genetics; D007987:Gonadotropin-Releasing Hormone / Q000097:blood; D006579:Heterozygote; D006801:Humans; D007984:Leydig Cell Tumor / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011629:Puberty, Precocious / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D011974:Receptors, LH / Q000235:genetics* / Q000378:metabolism; D013736:Testicular Neoplasms / Q000097:blood / Q000235:genetics* / Q000503:physiopathology
D009363:Neoplasm Proteins; D011974:Receptors, LH; D007987:Gonadotropin-Releasing Hormone