PMID- 10022417
OWN - NLM
STAT- MEDLINE
DCOM- 19990225
LR  - 20181201
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 84
IP  - 2
DP  - 1999 Feb
TI  - The same molecular defects of the gonadotropin-releasing hormone receptor
      determine a variable degree of hypogonadism in affected kindred.
PG  - 567-72
AB  - Detailed endocrinological studies were performed in the three affected kindred of
      a family carrying mutations of the GnRH receptor gene. All three were compound
      heterozygotes carrying on one allele the Arg262Gln mutation and on the other
      allele two mutations (Gln106Arg and Ser217Arg). When expressed in heterologous
      cells, both Gln106Arg and Ser217Arg mutations altered hormone binding, whereas
      the Arg262Gln mutation altered activation of phospholipase C. The propositus, a
      30-yr-old man, displayed complete idiopathic hypogonadotropic hypogonadism with
      extremely low plasma levels of gonadotropins, absence of pulsatility of
      endogenous LH and alpha-subunit, absence of response to GnRH and GnRH agonist
      (triptorelin), and absence of effect of pulsatile administration of GnRH. The two
      sisters, 24 and 18 yr old, of the propositus displayed, on the contrary, only
      partial idiopathic hypogonadotropic hypogonadism. They both had primary
      amenorrhea, and the younger sister displayed retarded bone maturation and uterus 
      development, but both sisters had normal breast development. Gonadotropin
      concentrations were normal or low, but in both cases were restored to normal
      levels by a single injection of GnRH. In the two sisters, there were no
      spontaneous pulses of LH, but pulsatile administration of GnRH provoked a
      pulsatile secretion of LH in the younger sister. The same mutations of the GnRH
      receptor gene may thus determine different degrees of alteration of gonadotropin 
      function in affected kindred of the same family.
FAU - de Roux, N
AU  - de Roux N
AD  - INSERM U-135 et Laboratoire d'Hormonologie et Biologie Moleculaire, Hopital de
      Bicetre, Le Kremlin Bicetre, France.
FAU - Young, J
AU  - Young J
FAU - Brailly-Tabard, S
AU  - Brailly-Tabard S
FAU - Misrahi, M
AU  - Misrahi M
FAU - Milgrom, E
AU  - Milgrom E
FAU - Schaison, G
AU  - Schaison G
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Receptors, LHRH)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 9002-67-9 (Luteinizing Hormone)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adult
MH  - Base Sequence
MH  - DNA/analysis/chemistry
MH  - Follicle Stimulating Hormone/metabolism
MH  - Gonadotropin-Releasing Hormone/administration & dosage
MH  - Humans
MH  - Hypogonadism/*genetics
MH  - Kinetics
MH  - Luteinizing Hormone/metabolism
MH  - Male
MH  - *Mutation
MH  - Pedigree
MH  - Periodicity
MH  - Receptors, LHRH/*genetics
MH  - Sequence Analysis
EDAT- 1999/02/18 00:00
MHDA- 1999/02/18 00:01
CRDT- 1999/02/18 00:00
PHST- 1999/02/18 00:00 [pubmed]
PHST- 1999/02/18 00:01 [medline]
PHST- 1999/02/18 00:00 [entrez]
AID - 10.1210/jcem.84.2.5449 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1999 Feb;84(2):567-72. doi: 10.1210/jcem.84.2.5449.