Auxological and endocrine phenotype in a population-based cohort of patients with PROP1 gene defects
Language English Country Great Britain, England Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
16131601
DOI
10.1530/eje.1.01989
PII: 153/3/389
Knihovny.cz E-resources
- MeSH
- Child MeSH
- DNA-Binding Proteins genetics MeSH
- DNA chemistry genetics MeSH
- Adult MeSH
- Phenotype MeSH
- Homeodomain Proteins genetics MeSH
- Pituitary Hormones deficiency MeSH
- Cohort Studies MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Adolescent MeSH
- Mutation * MeSH
- Pituitary Diseases genetics MeSH
- Polymerase Chain Reaction MeSH
- Retrospective Studies MeSH
- Sequence Analysis, DNA MeSH
- Aged MeSH
- Body Height physiology MeSH
- Transcription Factor Pit-1 MeSH
- Transcription Factors genetics MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DNA-Binding Proteins MeSH
- DNA MeSH
- HESX1 protein, human MeSH Browser
- Homeodomain Proteins MeSH
- Pituitary Hormones MeSH
- POU1F1 protein, human MeSH Browser
- Prophet of Pit-1 protein MeSH Browser
- Transcription Factor Pit-1 MeSH
- Transcription Factors MeSH
OBJECTIVE: Multiple pituitary hormone deficiency (MPHD) may result from defects of transcription factors that govern early pituitary development. We aimed to establish the prevalence of HESX1, PROP1, and POU1F1 gene defects in a population-based cohort of patients with MPHD and to analyse the phenotype of affected individuals. DESIGN AND METHODS: Genomic analysis was carried out on 74 children and adults with MPHD from the Czech Republic (including four sibling pairs). Phenotypic data were collected from medical records and referring physicians. RESULTS: One patient carried a heterozygous mutation of POU1F1 (71C > T), and 18 patients (including three sibling pairs) had a PROP1 mutation (genotypes 150delA/301delGA/9/, 301delGA/301-delGA/8/, or 301delGA/349T > A/1/). A detailed longitudinal phenotypic analysis was performed for patients with PROP1 mutations (n = 17). The mean ( +/-s.d.) birth length SDS of these patients (0.12 +/- 0.76) was lower than expected based on their mean ( +/-s.d.) birth weight SDS (0.63 +/- 1.27; P = 0.01). Parental heights were normal. The patients' mean ( +/-s.d.) height SDS declined to -1.5 +/- 0.9, -3.6 +/- 1.3 and -4.1 +/- 1.2 at 1.5, 3 and 5 years of age, respectively. GH therapy, initiated at 6.8 +/- 3.2 years of age (mean dose: 0.022 mg/kg per day), led to substantial growth acceleration in all patients. Mean adult height (n = 7) was normal when adjusted for mid-parental height. ACTH deficiency developed in two out of seven young adult patients. CONCLUSIONS: PROP1 defects are a prevalent cause of MPHD. We suggest that testing for PROP1 mutations in patients with MPHD might become standard practice in order to predict risk of additional pituitary hormone deficiencies.
References provided by Crossref.org
Etiology of combined pituitary hormone deficiency: GNAO1 as a novel candidate gene
Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes
