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

2015 ◽  
Vol 28 (9-10) ◽  
Author(s):  
Cecilia Lazea ◽  
Paula Grigorescu-Sido ◽  
Radu Popp ◽  
Marie Legendre ◽  
Serge Amselem ◽  
...  
Keyword(s):  
High Frequency ◽  
Bone Age ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Homozygous State ◽  
Pituitary Hormone Deficiency ◽  
Homozygous Genotype ◽  
Familial Form ◽  
History Of ◽  
Prop1 Gene

AbstractTo establish the frequency of the c.301_302 delAG mutation of theSomatic assessment, hormonal test, bone age, magnetic resonance imaging of the pituitary gland, and molecular diagnosis were performed in 26 patients with MPHD (7 patients with familial form of MPHD and 19 patients with sporadic form of MPHD).The c.301_302delAG mutation was detected in the homozygous state in 10 patients belonging to 5 unrelated families (7 patients with familial history of MPHD and 3 patients with sporadic form of MPHD). Those 10 patients presented variable pituitary hormone deficiency and pituitary morphology.The c.301_302delAG homozygous genotype had a high frequency of 38% (10/26), reaching 100% (7/7) in group with familial cases of MPHD and 16% (3/19) in group with sporadic forms of MPHD.

scholarly journals Molecular analysis of the PROP1 and HESX1 genes in patients with septo-optic dysplasia and/or pituitary hormone deficiency

2010 ◽  
Vol 54 (5) ◽  
pp. 482-487 ◽  
Author(s):  
Juliana B. Cruz ◽  
Vania S. Nunes ◽  
Sueli A. Clara ◽  
Denise Perone ◽  
Peter Kopp ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Genetic Alterations ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Pituitary Hormone Deficiency ◽  
Exon 1 ◽  
Genetic Mechanisms ◽  
Direct Sequence Analysis ◽  
Prop1 Gene ◽  
Pathogenic Process

OBJECTIVE: The present study aimed at evaluating the PROP1 and HESX1 genes in a group of patients with septo-optic dysplasia (SOD) and pituitary hormone deficiency (combined - CPHD; isolated GH deficiency - GHD). Eleven patients with a clinical and biochemical presentation consistent with CPHD, GHD or SOD were evaluated. SUBJECTS AND METHODS: In all patients, the HESX1 gene was analyzed by direct sequence analysis and in cases of CPHD the PROP1 gene was also sequenced. RESULTS: A polymorphism (1772 A > G; N125S) was identified in a patient with SOD. We found three patients carrying the allelic variants 27 T > C; A9A and 59 A > G; N20S in exon 1 of the PROP1 gene. Mutations in the PROP1 and HESX1 genes were not identified in these patients with sporadic GHD, CPHD and SOD. CONCLUSION: Genetic alterations in one or several other genes, or non-genetic mechanisms, must be implicated in the pathogenic process.

scholarly journals PROP1 gene analysis in Portuguese patients with combined pituitary hormone deficiency

2006 ◽  
Vol 65 (4) ◽  
pp. 479-485 ◽  
Author(s):  
Manuel C. Lemos ◽  
Leonor Gomes ◽  
Margarida Bastos ◽  
Valeriano Leite ◽  
Edward Limbert ◽  
...  
Keyword(s):  
Gene Analysis ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Pituitary Hormone Deficiency ◽  
Combined Pituitary Hormone Deficiency ◽  
Prop1 Gene

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.

scholarly journals Phenotypic Variability in Familial Combined Pituitary Hormone Deficiency Caused by a PROP1 Gene Mutation Resulting in the Substitution of Arg→Cys at Codon 120 (R120C)1

1998 ◽  
Vol 83 (10) ◽  
pp. 3727-3734 ◽  
Author(s):  
Christa Flück ◽  
Johnny Deladoey ◽  
Kuno Rutishauser ◽  
Andrée Eblé ◽  
ULRICH Marti ◽  
...  
Keyword(s):  
Phenotypic Variability ◽  
Failure To Thrive ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Pituitary Hormone Deficiency ◽  
Combined Pituitary Hormone Deficiency ◽  
Ames Dwarf ◽  
Hypothalamic Pituitary Axis ◽  
Prop1 Gene

As pituitary function depends on the integrity of the hypothalamic-pituitary axis, any defect in the development and organogenesis of this gland may account for a form of combined pituitary hormone deficiency (CPHD). A mutation in a novel, tissue-specific, paired-like homeodomain transcription factor, termed Prophet of Pit-1 (PROP1), has been identified as causing the Ames dwarf (df) mouse phenotype, and thereafter, different PROP1 gene alterations have been found in humans with CPHD. We report on the follow-up of two consanguineous families (n = 12), with five subjects affected with CPHD (three males and two females) caused by the same nucleotide C to T transition, resulting in the substitution of Arg→Cys in PROP1 at codon 120. Importantly, there is a variability of phenotype, even among patients with the same mutation. The age at diagnosis was dependent on the severity of symptoms, ranging from 9 months to 8 yr. Although in one patient TSH deficiency was the first symptom of the disorder, all patients became symptomatic by exhibiting severe growth retardation and failure to thrive, which was mainly caused by GH deficiency (n = 4). The secretion of the pituitary-derived hormones (GH, PRL, TSH, LH, and FSH) declined gradually with age, following a different pattern in each individual; therefore, the deficiencies developed over a variable period of time. All of the subjects entered puberty spontaneously, and the two females also experienced menarche and periods before a replacement therapy was necessary.

scholarly journals Genetic background of inherited multiple pituitary hormone deficiency. Mutations of PROP1 gene in Hungary

2011 ◽  
Vol 152 (6) ◽  
pp. 221-232
Author(s):  
Zita Halász
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Mutational Analysis ◽  
Hot Spot ◽  
Gene Mutations ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Multiple Pituitary Hormone Deficiency ◽  
Pituitary Hormone Deficiency ◽  
Prop1 Gene

In this work I analysed the outcome of growth hormone replacement treatment in patients with inherited form of multiple pituitary hormone deficiency and examined diseased-causing mutations of pituitary transcription factor genes which may underlie this disorder. The results showed that after treatment for a longer than 7-year period with a growth hormone preparation available under well-controlled distribution, the mean height of children with growth hormone deficiency reached the normal national reference range adjusted for age and sex. After establishment of clinical criteria for screening PROP1 gene mutations, I performed mutational analysis of all coding exons of this gene in 35 patients with inherited form of multiple pituitary hormone deficiency. With these studies, diseases-causing PROP1 gene mutations were detected in 15 of the 35 patients (43%). It was also found that more than 80% of mutant alleles were accounted for by those containing the 150delA and 301-302delGA mutations of the PROP1 gene. Importantly, these findings indicated a high relevance of mutational ”hot spots” of the PROP1 gene in Hungarian patients with inherited form of multiple pituitary hormone deficiency and they also offered an opportunity for the development of rational and cost-effective screening strategy. When clinical and hormonal findings of patients with and without PROP1 gene mutations were compared, results showed that growth hormone deficiency was diagnosed at earlier age of life in patients with PROP1 gene mutations, but the severity of growth retardation at the time of diagnosis of growth hormone deficiency or the age of patients at the time of manifestation of other pituitary hormone deficiencies (TSH, LH, FSH and ACTH) were similar in the two groups of patients. In 15 patients inherited form of multiple pituitary hormone deficiency who had no PROP1 gene mutations, exon 6 of the POU1F1 gene containing a mutational ”hot spot” was also examined but no mutations were found. Thus, these results do not support a significant role of the mutational ”hot spot” of the POU1F1 gene in Hungarian patients with inherited form of multiple pituitary hormone deficiency. Finally, I introduced a method for the detection of mutations of the PITX2 gene, a pituitary transcription factor that plays a role not only in pituitary development and differentiation but also in the lateralization of organs. With the use of this method, I performed mutational analysis of all coding exons of this gene in an exceptionally unique patient who had both situs inversus totalis and inherited form of multiple pituitary hormone deficiency, but no mutation was found. Thus, the findings in this patient failed to indicate that mutation of the PITX2 gene is involved in the pathomechanism of situs inversus totalis associated with inherited form of multiple pituitary hormone deficiency. Orv. Hetil., 2011, 152, 221–232.

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