A Limited Repertoire of Mutations of the Luteinizing Hormone (LH) Receptor Gene in Familial and Sporadic Patients with Male LH-Independent Precocious Puberty1
H. Kremer2,
J. W. M. Martens2,
M. van Reen,
M. Verhoef-Post,
J. M. Wit,
B. J. Otten,
S. L. S. Drop,
H. A. Delemarre-van de Waal,
M. Pombo-Arias,
F. De Luca,
N. Potau,
J. M. H. Buckler,
M. Jansen,
J. S. Parks,
H. A. Latif,
G. W. Moll,
W. Epping,
G. Saggese,
E. C. M. Mariman,
A. P. N. Themmen and
H. G. Brunner
Departments of Human Genetics (H.K., M.v.R., E.C.M.M., H.G.B.) and
Pediatrics (B.J.O.), University Hospital, 6500 HB Nijmegen, The
Netherlands; the Department of Endocrinology and Reproduction, Erasmus
University (J.W.M.M., M.V.-P., A.P.N.T.), 3000 DR Rotterdam, The
Netherlands; the Department of Pediatrics, University Hospital
(J.M.W.), Leiden, The Netherlands; the Department of Pediatrics, Sophia
Children’s Hospital (S.L.S.D.), 30156 Rotterdam, The Netherlands; the
Department of Pediatrics, Free University (H.A.D.-v.d.W.), 1081 HV
Amsterdam, The Netherlands; the Department of Pediatrics
(M.P.-A.), Hospital General de Galacia 15705 Santiago de
Compostella, Spain; the Department of Pediatrics, University Hospital
(F.D.L.), 90123 Messina, Italy; Hospital Materna-Infantil (N.P.), 08035
Barcelona, Spain; Department of Pediatrics, University of Leeds
(J.M.H.B.), Leeds, United Kingdom; Wilhelmina Children’s Hospital
(M.J.), 3501 CA Utrecht, The Netherlands; the Department of Pediatrics,
Emory University (J.S.P., H.A.L.), Atlanta, Georgia 30322; the
Department of Pediatrics, University of Mississippi Medical Center
(G.W.M.), Jackson, Mississippi 39216; the Department of
Pediatrics, University of Dusseldorf (W.E.), 40225 Dusseldorf, Germany;
and the Department of Pediatrics, University Hospital Pisa (G.S.),
56125 Pisa, Italy
Address all correspondence and requests for reprints to: Dr. H. G. Brunner, Department of Human Genetics, University Hospital Nijmegen, Postbox 9101, 6500 HB Nijmegen, The Netherlands. E-mail:
h.brunner{at}antrg.azn.nl
Herein, we report mutation analysis of the LH receptor genein 17 males
with LH-independent precocious puberty, of which8 were familial and 9
had a negative family history. A totalof 7 different mutations (all
previously reported) were detectedin 12 patients. Among 10 European
familial male-limited precociouspuberty (FMPP) patients who had a LH
receptor gene mutation,none had the Asp578Gly mutation,
which is responsible for thevast majority of cases in the U.S. The
restricted number ofactivating mutations of the LH receptor observed
in this andother studies of FMPP strongly suggests that an activating
phenotypeis associated with very specific sites in the receptor
protein.Clinical follow-up of the 5 patients who did not have LH
receptormutations shows that such cases most likely do not have true
FMPP.LH receptor mutation analysis provides a sensitive tool for
distinguishingtrue FMPP from other causes of early-onset
LH-independent pubertyin males.
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