Titre
Familial combined pituitary hormone deficiency due to a novel mutation R99Q in the hot spot region of Prophet of Pit-1 presenting as constitutional growth delay.
Type
article
Institution
Externe
Auteur(s)
Vieira, T.C.
Auteure/Auteur
Dias da Silva, M.R.
Auteure/Auteur
Cerutti, J.M.
Auteure/Auteur
Brunner, E.
Auteure/Auteur
Borges, M.
Auteure/Auteur
Arnaldi, L.T.
Auteure/Auteur
Kopp, P.
Co-dernière auteure/Co-dernier auteur
Abucham, J.
Auteure/Auteur
Liens vers les personnes
ISSN
0021-972X
Statut éditorial
Publié
Date de publication
2003-01
Volume
88
Numéro
1
Première page
38
Dernière page/numéro d’article
44
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Combined pituitary hormone deficiency (CPHD) is characterized by impaired production of GH and one or more of the other anterior pituitary hormones. Prophet of Pit-1 (PROP-1), one of the pituitary specific homeodomain transcription factors, is involved in the differentiation of the anterior pituitary cells (somatotrophs, lactotrophs, thyrotrophs, and gonadotrophs), and PROP-1 gene mutations may interfere with the development of these cells, resulting in CPHD. We performed molecular analyses of the PROP-1 gene in two siblings, born to consanguineous parents, who presented with short stature. The index patient, a boy, was initially diagnosed with constitutional growth delay based on familial short stature, low parental target height, normal GH secretion, and imaging of the pituitary gland. On follow-up, auxological data and pubertal delay prompted a thorough reevaluation, which documented GH, TSH, and gonadotropin deficiencies. Direct sequencing of the PROP-1 gene revealed a novel homozygous transition 296G-->A in exon 2 in the two affected siblings. The mutation substitutes a highly conserved arginine by a glutamine at codon 99 (R99Q) in the second helix of the DNA-binding domain of the PROP-1 protein. Compared with wild-type PROP-1, R99Q displays a significant decrease in DNA binding on a paired box response element (PRDQ9) and trans-activation of a luciferase reporter gene. The findings emphasize the importance of repeated evaluations and illustrate that patients with CPHD associated with PROP-1 mutations present with a phenotypic spectrum, suggesting that the consequences of distinct PROP-1 mutations may be diverse and/or that additional factors, such as modifier genes, may have an impact on their expressivity.
Sujets
PID Serval
serval:BIB_A94D1CCA9C98
PMID
Open Access
Oui
Date de création
2020-12-30T13:44:06.077Z
Date de création dans IRIS
2025-05-20T23:42:10Z