Molecular analysis of brazilian patients with combined pituitary hormone deficiency and orthotopic posterior pituitary lobe reveals eight different PROP1 alterations with three novel mutations

2017 ◽  
Vol 87 (6) ◽  
pp. 725-732 ◽  
Author(s):  
Joao LO Madeira ◽  
Mirian Y Nishi ◽  
Marilena Nakaguma ◽  
Anna F Benedetti ◽  
Isabela Peixoto Biscotto ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Posterior Pituitary ◽  
Novel Mutations ◽  
Pituitary Hormone Deficiency ◽  
Combined Pituitary Hormone Deficiency ◽  
Posterior Pituitary Lobe

scholarly journals Novel Mutations within the POU1F1 Gene Associated with Variable Combined Pituitary Hormone Deficiency

2005 ◽  
Vol 90 (8) ◽  
pp. 4762-4770 ◽  
Author(s):  
James P. G. Turton ◽  
Rachel Reynaud ◽  
Ameeta Mehta ◽  
John Torpiano ◽  
Alexandru Saveanu ◽  
...  
Keyword(s):  
Dna Binding ◽  
Mutational Analysis ◽  
Hot Spot ◽  
Dominant Negative ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Novel Mutations ◽  
Pituitary Hormone Deficiency ◽  
Combined Pituitary Hormone Deficiency ◽  
Functional Studies

Context: Mutations within the gene encoding the pituitary-specific transcription factor POU1F1 are associated with combined pituitary hormone deficiency (CPHD). Most of the affected individuals manifest GH, prolactin, and TSH deficiency. Objective: We have now screened 129 individuals with CPHD and isolated GH deficiency for mutations within POU1F1. Results: Causative mutations were identified in 10 of 129 individuals (7.8%). Of these, five patients harbored the dominant negative R271W mutation, which is a well-recognized mutational hot spot. We have also identified a second frequently occurring mutation, E230K, which appears to be common in Maltese patients. Additionally, we describe two novel mutations within POU1F1, an insertion of a single base pair (ins778A) and a missense mutation (R172Q). Functional studies have revealed that POU1F1 (E230K) is associated with a reduction in transactivation, although DNA-binding affinity is similar to the wild-type protein. On the other hand, POU1F1 (R172Q) is associated with a reduction in DNA binding and transactivation, whereas POU1F1 (ins778A) is associated with loss of DNA binding and a reduction in transactivation. Conclusions: Our data suggest that the phenotype associated with POU1F1 mutations may be more variable, with the occasional preservation of TSH secretion. Additionally, our data revealed POU1F1 mutations in three patients who were diagnosed as having ACTH deficiency but who, on further evaluation, were found to have normal cortisol secretion. Hence, elucidation of the genotype led to further evaluation of the phenotype, with the cessation of cortisol replacement that had been commenced unnecessarily. These data reflect the importance of mutational analysis in patients with CPHD.

scholarly journals Combined Pituitary Hormone Deficiency Caused by Compound Heterozygosity for Two Novel Mutations in the POU Domain of the PIT1/POU1F1 Gene1

2001 ◽  
Vol 86 (4) ◽  
pp. 1545-1550 ◽  
Author(s):  
Brenda I. Hendriks-Stegeman ◽  
Kevin D. Augustijn ◽  
Bert Bakker ◽  
Pieternella Holthuizen ◽  
Peter C. van der Vliet ◽  
...  
Keyword(s):  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Compound Heterozygosity ◽  
Novel Mutations ◽  
Pituitary Hormone Deficiency ◽  
Combined Pituitary Hormone Deficiency ◽  
Pou Domain

Molecular analysis of novelPROP1mutations associated with combined pituitary hormone deficiency (CPHD)

2009 ◽  
Vol 70 (1) ◽  
pp. 96-103 ◽  
Author(s):  
D. Kelberman ◽  
J. P. G. Turton ◽  
K. S. Woods ◽  
A. Mehta ◽  
M. Al-Khawari ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Pituitary Hormone Deficiency ◽  
Combined Pituitary Hormone Deficiency

scholarly journals Molecular analysis of PROP1, PIT1, HESX1, LHX3, and LHX4 shows high frequency of PROP1 mutations in patients with familial forms of combined pituitary hormone deficiency

2007 ◽  
Vol 51 (7) ◽  
pp. 1097-1103 ◽  
Author(s):  
Teresa C. Vieira ◽  
Valter T. Boldarine ◽  
Julio Abucham
Keyword(s):  
Transcription Factor ◽  
High Frequency ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Posterior Pituitary ◽  
Developmental Gene ◽  
Pituitary Hormone Deficiency ◽  
Combined Pituitary Hormone Deficiency ◽  
Prevalent Disease ◽  
Genetic Form

Combined Pituitary Hormone Deficiency (CPHD) is a prevalent disease in Neuroendocrinology services. The genetic form of CPHD may originate from mutations in pituitary transcription factor (PTF) genes and the pituitary image in these cases may give a clue of what PTF is most probably mutated: defects in LHX4 are usually associated with ectopic posterior pituitary (EPP); defects in LHX3, PIT1, and PROP1, with normally placed posterior pituitary (NPPP); HESX1 mutations are associated with both. OBJECTIVE: To identify mutations in PTF genes in patients with idiopathic hypopituitarism followed in our service, based on the presence or absence of EPP on sellar MRI. METHODS: Forty patients with idiopathic hypopituitarism (36 families, 9 consanguineous), followed in the Neuroendocrinology Outpatient Clinic of UNIFESP, Brazil, were submitted to sequencing analyses of PTF genes as follows: LHX3, HESX1, PIT1, and PROP1 were sequenced in patients with NPPP (26/40) and HESX1 and LHX4 in patients with EPP (14/40). RESULTS: We identified only PROP1 mutations in 9 out of 26 patients with CPHD and NPPP (35%). Since eight of them came from 4 consanguineous families, the prevalence of PROP1 mutations was higher when only consanguineous families were considered (44%, 4/9). At the end of the study, we decided to sequence PROP1 in patients with EPP, just to confirm that they were not candidates for PROP1 mutations. No patients with EPP had PROP1 or other PTF mutations. CONCLUSIONS: Patients with idiopathic CPHD and NPPP, born from consanguineous parents, are the strong candidates for PROP1 mutations. Other developmental gene(s) may be involved in the genesis of idiopathic hypopituitarism associated with EPP.

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