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Novel mutations within PROP1 associated with Combined Pituitary Hormone Deficiency (CPHD)
No full textThe N-terminus of the transcriptional repressor HESX1 facilitates interaction with the homeodomain activator PROP1
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Molecular analysis of novel PROP1 mutations associated with combined pituitary hormone deficiency (CPHD)
No full textMutations in PROP1 are a frequent cause of familial CPHD. We have described four novel mutations in PROP1 in 3 pedigrees, all resulting in PROP1 deficiency by different mechanisms. The phenotypic variation observed in association with PROP1 mutations both within and between families, together with the evolving nature of hormone deficiencies and sometimes changing pituitary morphology indicates a need for continual monitoring of these patients
In vitro studies of dominant negative PIT1 mutant protei
No full textMutations in the Pit1 gene severely affect the development and function of the anterior
pituitary gland in both mice and humans, resulting in deficiencies of growth hormone,
prolactin and thyroid stimulating hormone. These hormone deficiencies are thought to
result from the failure to specify the identity of cells, presumably through the inability
to activate genes that encode hormones. Furthermore, hypoplasia of the pituitary gland
may result from the inability of pituitary endocrine cells to proliferate. The aim of this
project is to study the effect of dominant Pit1 gene mutations to determine the
mechanism of action of the mutant proteins. The study of mutant PIT1 proteins should
allow greater understanding of how wild type PIT1 protein functions. Luciferase
reporter assays were used to test the transcriptional activity of dominant negative PIT1
mutant proteins on different target promoters. These assays showed that the mutations
had cell and reporter specific effects on luciferase activity that may be due to the
combined effects of both direct transcriptional repression and indirect off-target effects,
perhaps negative effects on cell viability. Several of the mutations resulted in increased
activity in a reporter and cell type specific manner. Mutation of the N-terminal
transactivation domain affected protein stability and electrophoretic mobility, strongly
suggesting an effect on post-translational modification. However, subsequent analysis
was unable to confirm this. Additionally, two novel recessively inhertited mutations
were identified in a patient with combined pituitary hormone deficiency. The IVS1+3nt
(a>g) mutation severely affected splice donor site definition whereas the R265W
missense mutation resulted in reduced protein expression
Over and under dosage of the transcription factor SOX3 can be associated with X-linked hypopituitarism in the absence of mental retardation
No full textMutations within HESX1 in CPHD/IGHD are associated with impaired repression due to compromised interaction with the Groucho co-repressor
No full textDuplication and polyalanine tract expansion within SOX3 associated with X-linked panhypopituitarism in the absence of mental retardation (MR)
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Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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