Mutations in the genes encoding pituitary transcription factors (mainly PROP1, POUF1 and HESX1) are responsible for familial combined pituitary hormone deficiency (CPHD) and septo-optic dysplasia (SOD) while only a low percentage of mutations are the cause of sporadic forms.
This is the first report of a mutation in the initiation codon of the PROP1 gene and this further expands the spectrum of known mutations responsible for CPHD.
In conclusion, these two siblings of different sexes with CPHD carrying the 301-302delAG mutation in the Prop1 gene presented a variable phenotype characterized by GH, TSH, LH and FSH deficiency.
PROP1 gene mutations appear to be frequently responsible for CPHD, particularly in Middle and Eastern Europe and the Americas, but few cases have been reported in Japan.
Clinical follow-up and molecular analysis of PROP1 in two adult brothers with CPHD, born from consanguineous parents, and not treated until late adulthood.
We screened a cohort of sporadic (n = 189) and familial (n = 44) patients with hypopituitarism (153 CPHD and 80 isolated hormone deficiencies) for mutations within the coding sequence of PROP1.
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.
As the most common gene alterations responsible for CPHD are within either the PROP-1- or the POU1F1- (PIT-1)-gene these two genes were further studied.
This study analyses the POU1F1 and PROP1 genes in a cohort of Australian children with combined pituitary hormone deficiency (CPHD) and correlates results with patient phenotype.
Because both patients have the same PROP-1 mutations and an identical pattern of combined pituitary hormone deficiency, we suggest that early pituitary enlargement may be the typical course in such patients in whom pituitary surgery is not indicated.
These data show that PROP1 mutations can result in panhypopituitarism, the most severe form of AP deficiency, in which the production of all hormones is compromised and support a role for PROP1 in the maintenance and/or differentiation of all five hormone-secreting cell types.
Mutations of the pituitary transcription factor Prop-1, which is responsible for the syndrome of Ames dwarfism in mice, are being increasingly recognized as a cause of combined pituitary hormone deficiency in humans, although ACTH deficiency has been described only once.
The prophet of Pit-1 gene (PROP1), a novel pituitary-specific homeodomain factor, has been proved to be one of the causative genes for combined pituitary hormone deficiency (CPHD).
A novel type of pituitary-specific transcription factor, Prophet of Pit-1 (Prop-1) gene (PROP1), expresses in just early embryonic stage in mouse and closely related as a causative gene in combined pituitary hormone deficiency.