October - December 2010, Volume 6, Issue 4

Ghervan C, Stroe M, Olarescu C, Ghervan L, Duncea I, Legendre M, Young J

C.301-302delAG mutation in the PROP 1 gene as molecular basis of progressive combined pituitary hormone deficiency in two Romanian brothers

Acta Endo (Buc) 2010, 6 (4): 401-412
doi: 10.4183/aeb.2010.401

The appearance and normal development of the anterior pituitary gland requires several signalling molecules and specific transcription factors. Gene mutations of these\r\npituitary transcription factors may lead to different degrees of combined pituitary hormone deficiency (CPHD) associated or not with morphological changes of the hypothalamicpituitary region. We present the first Romanian case of progressive CPHD in two brothers from a consanguineous family. Clinical, hormonal and MRI follow-up were performed during 20 years. Growth hormone deficiency was certified at the age of 5, respectively 3 years, followed by gonadotropin deficiency diagnosed at the age of 21, respectively 19 years, and by central hypothyroidism diagnosed at the age of 23, respectively 21 years.\r\nSubstitutive treatment rhGH was commenced, followed by testosterone and later thyroxin, in adequate doses. Adrenal function was normal during the follow-up. MRI revealed\r\nanterior pituitary hypoplasia in both siblings, with a partially empty sella in the younger brother and a thick midline septum in the sphenoid sinus in both siblings, which was not described in previous reports. The progressive CPHD suggested a PROP 1 deficiency, which was confirmed by genetic analysis. The c.301-302delAG homozygous mutation in the PROP 1 gene was identified, resulting in a complete loss of promoter binding and\r\ntranscriptional activation of the mutant protein.

Keywords: progressive combined pituitary hormone deficiency, c.301-302delAG mutation in PROP1 gene, septum of sphenoid sinus

Correspondence: Cristina Ghervan MD, University of Medicine and Pharmacy - Endocrinology; 3 Pasteur, Cluj-Napoca 400349, Romania, Tel: +40264 431576, Fax: +40264 431576 Email: cghervan@yahoo.com