Functional SNPs within the Intron 1 of the PROP1 Gene Contribute to Combined Growth Hormone Deficiency (CPHD)

Godi, Michela; Mellone, Simona; Tiradani, L.; Marabese, Rita; Bardelli, Claudio; Salerno, Mariacarolina; Prodam, Flavia; Bellone, Simonetta; Petri, Antonella; Momigliano–Richiardi, Patricia; Bona, Gianni; Giordano, Mara

doi:10.1210/jc.2012-1527

Cited by 4 publications

(6 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since defects in the regulatory regions of a gene can alter expression of the gene, variations in regulatory regions of pituitary transcription factors are likely to also cause isolated or combined pituitary hormone deficiencies. This is supported by the work of Godi et al [ 7 ], who found an association between two polymorphisms within and around a regulatory region in the intron 1 of PROP1 (rs73346254A and rs148607624 delTAG), and combined pituitary hormone deficiencies (CPHD). Co-presence of the alternative alleles of both SNPs was associated with reduced transcriptional activity as shown by a decreased luciferase activity.…”

Section: Introductionmentioning

confidence: 62%

“…We did not find any variants in the HESX1 promoter in either the (p)IGHD or CPHD patients. Four of the PROP1 promoter SNPs have been previously reported by Godi et al [ 7 ]. The genotype frequencies did not differ significantly from the frequencies found in healthy controls from the 1000 Genome Project (Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…Nucleotide sequences were obtained from Ensembl ( PROP1 : ENSG00000175325; POU1F1 ENSG00000064835; HESX1 ENSG00000163666). Primer sequences for CEA and CEB of PROP1 were kindly provided by Godi et al [ 7 ] and Ward et al [ 30 ]. An overview of the regulatory regions of PROP1, POU1F1 and HESX1 is shown in Fig.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Genetic screening of regulatory regions of pituitary transcription factors in patients with idiopathic pituitary hormone deficiencies

et al. 2017

View full text Add to dashboard Cite

PurposeMutation frequencies of PROP1, POU1F1 and HESX1 in patients with combined pituitary hormone deficiencies (CPHD) vary substantially between populations. They are low in sporadic CPHD patients in Western Europe. However, most clinicians still routinely send DNA of their CPHD patients for genetic screening of these pituitary transcription factors. Before we can recommend against screening of PROP1, POU1F1 and HESX1 as part of routine work-up for Western-European sporadic CPHD patients, it is crucial to rule out possible defects in regulatory regions of these genes, which could also disturb the complex process of pituitary organogenesis.MethodsThe regulatory regions of PROP1, POU1F1 and HESX1 are not covered by Whole Exome Sequencing as they are largely located outside the coding regions. Therefore, we manually sequenced the regulatory regions, previously defined in the literature, of PROP1, POU1F1 and HESX1 among 88 Dutch patients with CPHD. We studied promoter SNPs in relation to phenotypic data.ResultsWe found six known SNPs in the PROP1 promoter. In the POU1F1 promoter, we found one new variant and two known SNPs. We did not find any variant in the HESX1 promoter.ConclusionAlthough the new POU1F1 variant might explain the phenotype of one patient, the general conclusion of this study is that variants in regulatory regions of PROP1, POU1F1 and HESX1 are rare in patients with sporadic CPHD in the Netherlands. We recommend that genetic screening of these pituitary transcription factors should no longer be part of routine work-up for Western-European, and especially Dutch, sporadic CPHD patients.Electronic supplementary materialThe online version of this article (10.1007/s11102-017-0850-6) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 62%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Genetic screening of regulatory regions of pituitary transcription factors in patients with idiopathic pituitary hormone deficiencies

et al. 2017

View full text Add to dashboard Cite

show abstract

“…This finding can be explained by the genetic heterogenity of the disease, by a multifactorial etiology determined by low penetrance genetic factors, or by phenocopies resulting from unknown acquired causes (34,36) .…”

Section: Discussionmentioning

confidence: 99%

The c.301_302delAG PROP1 gene mutation in Romanian patients with multiple pituitary hormone deficiency

Lazea¹,

Grigorescu-Sido

Popp

et al. 2015

Journal of Pediatric Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…Importantly, ATBF1 not only activates expression of Pit1 gene though interacting with Pit1 enhancer ( Qi et al, 2008 ), but also potentially synergizes with PROP1 that can bind to the enhancer of Pit1 gene and regulate the expression levels of growth hormone, prolactin, and TSH-β ( Carvalho et al, 2006 ; Davis et al, 2010 ; Araujo et al, 2013 ). STAT3 , Pit1 , and PROP1 genes play an important role in embryo early development and cell differentiation ( Zhong et al, 1994 ; Schindler et al, 1995 ; Darnell, 1997 ; Heinrich et al, 1998 ; Shuai et al, 1999 ; Kamohara et al, 2000 ; Fang et al, 2012 ; Godi et al, 2012 ; Akcay et al, 2013 ; Pan et al, 2013 ; Navardauskaite et al, 2014 ), so ATBF1 gene was hypothesized to produce important effects on early development and cell differentiation, thus it would affect the grow traits in animals.…”

Section: Introductionmentioning

confidence: 99%

Novel Nucleotide Variations, Haplotypes Structure and Associations with Growth Related Traits of Goat AT Motif-Binding Factor (<i>ATBF1</i>) Gene

Zhang

Wei

et al. 2015

Asian Australas. J. Anim. Sci

View full text Add to dashboard Cite

The AT motif-binding factor (ATBF1) not only interacts with protein inhibitor of activated signal transducer and activator of transcription 3 (STAT3) (PIAS3) to suppress STAT3 signaling regulating embryo early development and cell differentiation, but is required for early activation of the pituitary specific transcription factor 1 (Pit1) gene (also known as POU1F1) critically affecting mammalian growth and development. The goal of this study was to detect novel nucleotide variations and haplotypes structure of the ATBF1 gene, as well as to test their associations with growth-related traits in goats. Herein, a total of seven novel single nucleotide polymorphisms (SNPs) (SNP 1-7) within this gene were found in two well-known Chinese native goat breeds. Haplotypes structure analysis demonstrated that there were four haplotypes in Hainan black goat while seventeen haplotypes in Xinong Saanen dairy goat, and both breeds only shared one haplotype (hap1). Association testing revealed that the SNP2, SNP5, SNP6, and SNP7 loci were also found to significantly associate with growth-related traits in goats, respectively. Moreover, one diplotype in Xinong Saanen dairy goats significantly linked to growth related traits. These preliminary findings not only would extend the spectrum of genetic variations of the goat ATBF1 gene, but also would contribute to implementing marker-assisted selection in genetics and breeding in goats.

show abstract

Functional SNPs within the Intron 1 of the PROP1 Gene Contribute to Combined Growth Hormone Deficiency (CPHD)

Abstract: Variations with a functional significance conferring susceptibility to CPHD have been identified in the PROP1 gene, indicating a multifactorial origin of this disorder in sporadic cases.

Cited by 4 publications

References 16 publications

Genetic screening of regulatory regions of pituitary transcription factors in patients with idiopathic pituitary hormone deficiencies

Genetic screening of regulatory regions of pituitary transcription factors in patients with idiopathic pituitary hormone deficiencies

The c.301_302delAG PROP1 gene mutation in Romanian patients with multiple pituitary hormone deficiency

Novel Nucleotide Variations, Haplotypes Structure and Associations with Growth Related Traits of Goat AT Motif-Binding Factor (<i>ATBF1</i>) Gene

Contact Info

Product

Resources

About