PROP1 Gene Screening in Patients with Multiple Pituitary Hormone Deficiency Reveals Two Sites of Hypermutability and a High Incidence of Corticotroph Deficiency
S. Vallette-Kasic,
A. Barlier,
C. Teinturier,
A. Diaz,
M. Manavela,
F. Berthezène,
P. Bouchard,
J. L. Chaussain,
R. Brauner,
I. Pellegrini-Bouiller,
P. Jaquet,
A. Enjalbert and
T. Brue
Department of Endocrinology (S.V.-K., P.J., T.B.), Centre
Hospitalier Universitaire (CHU) Timone, Marseille, France 13385;
Laboratoire ICNE (S.V.-K., A.B., A.D., M.M., I.P.-B., P.J., A.E.,
T.B.), CNRS UMR 6544, IFR Jean Roche, Marseille,
France;
Department of Endocrinology (C.T., J.L.C.), Hôpital Saint Vincent
de Paul, 75014 Paris, France; Department of Endocrinology (F.B.),
Hôpital de l’Antiquaille, 69005 Lyon, France; Department of
Endocrinology (P.B.), Hôpital Saint Antoine, 75012 Paris,
France; and Department of Endocrinology (R.B.), Hôpital
Necker-Enfants Malades, 75015 Paris, France
Address all correspondence and requests for reprints to: Thierry Brue, M.D., Ph.D., Hopital de la Timone, 264 rue St. Pierre, 13385 Marseille Cedex 5, France. E-mail tbrue{at}ap-hm.fr
Abstract
Alterations of the gene encoding the pituitary transcriptionfactor
PROP1 were associated with congenital forms of multiplepituitary
hormone deficiencies in several families. Among 23patients with
multiple pituitary hormone deficiencies screenedfor a
PROP1 gene abnormality, nine belonging to eight
unrelatedfamilies had homozygous PROP1 gene defects.
All mutations werelocated in exon 2 and affected only two different
sites: a homozygousAG deletion at codons 99/100/101 (n = 5);
homozygous point mutationsaffecting codon 73: R73C (n = 2) or
R73H (n = 1), and a R73C/R99Xdouble-heterozygous mutation (n
= 1). R73H and R99X were neverdescribed. All patients were born to
unaffected parents, andconsanguinity was documented in two patients.
They had completeGH, LH-FSH, and TSH deficiencies and normal basal
levels ofPRL. Delayed ACTH deficiency was diagnosed in four of nine
patients.At magnetic resonance imaging the anterior pituitary was
hypoplasticin seven patients and hyperplastic in two. This study found
twonovel mutations (R73H and R99X) and underlines the high incidence
ofPROP1 gene alterations in patients with multiple
pituitary hormonedeficiencies. A corticotroph deficiency was
frequently observedin association with GH, TSH, and gonadotropin
deficiencies andshould be carefully sought during follow-up.
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