ECE2014 Poster Presentations Pituitary Clinical (<emphasis role="italic">Generously supported by IPSEN</emphasis>) (108 abstracts)
Population-based cohort study: PROP1 gene mutations are the most prevalent cause of congenital multiple pituitary hormone deficiency in Lithuania
Ruta Navardauskaite 1 , Petra Dusatkova 3 , Barbora Obermannova 3 , Roland W Pfaeffle 4 , Werner F Blum 4 , Dalia Adukauskiene 2 , Natalija Smetanina 1 , Ondrej Cinek 3 , Rasa Verkauskiene 1 & Jan Lebl 3
1Institute of Endocrinology of Lithuanian University of Health Sciences, Kaunas, Lithuania; 2Medical Academy of Lithuanian University of Health Sciences, Kaunas, Lithuania; 3Department of Pediatrics, Second Faculty of Medicine, Charles University in Prague and University Hospital Prague–Motol, Prague, Czech Republic; 4University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
Introduction: Congenital multiple pituitary hormone deficiency (MPHD) may result from defects of transcription factors that govern the early pituitary development. The most prevalent are two mutation of PROP1 gene: the c.296delGA and c.150delA.
Methods: Seventy-five Lithuanian MPHD patients were tested for PROP1 defects. Perinatal and postnatal data were obtained from medical records. Hormonal investigations, pituitary imaging and GH therapy were performed at a single centre in Kaunas.
The PROP1 gene was investigated by Sanger sequencing. Ancestral origin of mutation was assessed by genotyping of 22 single nucleotide polymorphisms flanking the PROP1 gene, and their haplotype analysis.
Results: Fifty-two subjects (69.3%; 28 males; including ten sibling pairs and two sibling triples) from 38 families were found to carry a biallelic PROP1 gene mutation. Fifty of these were homozygous 296delGA and two were compound heterozygotes 296delGA/R71H and 296delGA/150delA. We found the highest rate of PROP1 mutations among MPHD patients from populations studied so far (17.5 per million).
Patients’ birth lengths/weights were normal. Height declined to S.D. −1.56, −2.34, −3.43, −3.52, and −3.70 (medians) at years 1–5. Deficiencies of GH, TSH, ACTH, and FSH/LH were diagnosed in 50/52, 52/52, 21/52, and 25/52 subjects at median age 5.5; 5.6; 13.1, and 15.0 years respectively. Pituitary height ranged from 16.6 (+20.2 S.D.) to 1.4 mm (−15.5 S.D.) and declined with age (r2=0.27, P=0.001). GH therapy increased growth rates to 12.2; 9.1; 6.9; 6.8; 6.7; 5.6, and 5.7 cm/year (medians).
The mutation carriers were found to share a common ancestor with the c.296delGA mutation having arisen about 112 generations ago (P≤3×10−4).
Conclusions: The population-based cohort of patients with PROP1 gene mutation is the largest described so far. High prevalence of PROP1 defects in Lithuania is due to a founder effect of c.296delGA mutation.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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