[A report of familial male-limited precocious puberty caused by a germ-line heterozygous mutation (M398T) in luteinizing hormone receptor gene].
ABSTRACT To clarify the possible gene mutations in luteinizing hormone(LH) receptor gene in a boy with LH independent precocious puberty and probe the mechanism the of diseases caused by LH receptor activating mutations.
(1) Describe the clinical manifestations and laboratory data in a 5-year-old boy with LH independent precocious puberty. (2) Peripheral leukocytes were collected from the proband, his parents and other 20 normal puberty developed males. PCR and direct DNA sequence of 11 exons in LH receptors gene were conducted.
(1) The proband was diagnosed to have LH independent precocious puberty according to the clinical symptoms and the laboratory tests. (2) A germ-line heterozygous point mutation in the 11 exon of LH receptor gene was found in the proband and his mother: c1193 T-->C leading to amino acid change with M398T, which causes consecutively an activation of the LH receptor. (3) Other nucleotide changes in the proband and other normal males include c935 A-->G (N312S) and c1065 -->C (same sense mutation).
(1) A germ-line heterozygous point mutation in the LH receptor gene with M398T leads to consecutively activation of the LH receptor and LH independent precocious puberty. (2) The same point mutation does not have any influence on the puberty development, menstruation and productive functions of the proband's mother. (3) The LH receptor gene has possible polymorphism in the Han ethnic population.
- [Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND In recent years it became evident that several types of the luteinizing hormone/choriogonadotrophin receptor (LHCGR) exist. In addition to the classical receptor type known in rodents, an LHCGR type containing an additional exon is present in primates and humans. This specific exon 6A introduces a hitherto unknown regulatory pathway of the LHCGR at the transcriptional level which can lead to the expression of an alternative protein covering the extracellular part only. Furthermore, an LHCGR type lacking exon 10 at the mRNA and protein levels has been described in the New World primate lineage, giving rise to an additional receptor type in which amino acids of the extracellular hinge region connecting the leucine-rich repeat domain and transmembrane domain are missing.METHODS Topic-related information was retrieved by systematic searches using Medline/PubMed. Structural homology models were retrieved from a glycoprotein hormone receptors web application and from recent publications.RESULTSIn a novel approach, we combine functional aspects with three-dimensional properties of the LHCGR and the different receptor types to deduce causative relationships between these two parameters. On this basis, the physiological impact and patho-physiological consequences of the different LHCGR types are inferred.CONCLUSIONS The complex system of different LHCGR types and two corresponding hormones (LH and CG) represents a major challenge for future studies on selective hormone binding, signal transduction and receptor regulation. The presence of these naturally occurring LHCGR types requires re-examining of our present view on receptor function, experimental set-ups and data interpretation, but also offers new clinical approaches to interfere with LH/CG action in humans.Human Reproduction Update 05/2013; DOI:10.1093/humupd/dmt023 · 8.66 Impact Factor