Katica Bajuk Studen1, Magdalena Avbelj Stefanija2, Alexandru Saveanu3,4, Anne Barlier3,4,5, Thierry Brue4,5, Marija Pfeifer6. 1. Department of Nuclear Medicine, University Medical Centre Ljubljana, Zaloška 7, 1000, Ljubljana, Slovenia. katica.bajuk@kclj.si. 2. Department of Pediatric Endocrinology, Diabetes and Metabolism, University Children's Hospital, University Medical Centre Ljubljana, Bohoriceva 20, 1000, Ljubljana, Slovenia. 3. Assistance Publique-Hôpitaux de Marseille (AP-HM), Laboratory of Molecular Biology, Hôpital de la Conception, 13005, Marseille, France. 4. Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical Genetics (MMG), Marseille, France. 5. Assistance Publique-Hôpitaux de Marseille (AP-HM), Centre de Référence des Maladies Rares de l'hypophyse HYPO, Department of Endocrinology, Hôpital de la Conception, 13005, Marseille, France. 6. Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia.
Abstract
PURPOSE: Among genetic causes of combined pituitary hormone deficiency (CPHD), mutations of genes coding for transcription factors involved in pituitary development have been implicated. Congenital CPHD is a rare disease; therefore, it is important to expand the knowledge about incidence and regional distribution of specific mutations. The aim of this paper is to report results of genetic analyses of adult Slovenian patients with CPHD. METHODS: Twenty-three adult Slovenian patients with early childhood onset CPHD were included in the study. Blood samples were collected through the GENHYPOPIT network to assess possible mutations of six genes (PROP1/HESX1/LHX4/LHX3/POU1F1) involved in the pituitary development following an established algorithm. RESULTS: In seven out of 23 patients (30%) a specific mutation in genes encoding pituitary transcription factors was discovered. In five patients, two different mutations of the PROP1 gene (c.150delA and c.301-302delAG) were identified. One patient was heterozygous for a missense variant in the LHX4 gene. Additionally, one patient was positive for a mutation in the gene coding for prokineticin receptor-2. CONCLUSIONS: Our study confirms that the two most common mutations of the PROP1 gene globally are also the most frequent mutations in the cohort of adult Slovenian patients with CHPD. Other mutations of pituitary transcription factor genes are extremely rare.
PURPOSE: Among genetic causes of combined pituitary hormone deficiency (CPHD), mutations of genes coding for transcription factors involved in pituitary development have been implicated. Congenital CPHD is a rare disease; therefore, it is important to expand the knowledge about incidence and regional distribution of specific mutations. The aim of this paper is to report results of genetic analyses of adult Slovenian patients with CPHD. METHODS: Twenty-three adult Slovenian patients with early childhood onset CPHD were included in the study. Blood samples were collected through the GENHYPOPIT network to assess possible mutations of six genes (PROP1/HESX1/LHX4/LHX3/POU1F1) involved in the pituitary development following an established algorithm. RESULTS: In seven out of 23 patients (30%) a specific mutation in genes encoding pituitary transcription factors was discovered. In five patients, two different mutations of the PROP1 gene (c.150delA and c.301-302delAG) were identified. One patient was heterozygous for a missense variant in the LHX4 gene. Additionally, one patient was positive for a mutation in the gene coding for prokineticin receptor-2. CONCLUSIONS: Our study confirms that the two most common mutations of the PROP1 gene globally are also the most frequent mutations in the cohort of adult Slovenian patients with CHPD. Other mutations of pituitary transcription factor genes are extremely rare.
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