Endocrine https://doi.org/10.1007/s12020-019-01949-2 ORIGINAL ARTICLE Genetic analysis of adult Slovenian patients with combined pituitary hormone deficiency Katica Bajuk Studen 1 ● Magdalena Avbelj Stefanija 2 ● Alexandru Saveanu 3,4 ● Anne Barlier 3,4,5 ● Thierry Brue 4,5 ● Marija Pfeifer 6 Received: 10 February 2019 / Accepted: 4 May 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Purpose Among genetic causes of combined pituitary hormone deficiency (CPHD), mutations of genes coding for tran- scription 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 dis- covered. 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. Keywords Pituitary ● Hypopituitarism ● CPHD ● PROP1 ● LHX4 Introduction Congenital hypopituitarism encompasses a group of dif- ferent disorders and may manifest as an isolated hormone deficiency, or alternatively several pituitary axes may be defective resulting in combined pituitary hormone defi- ciency (CPHD) [1]. Among the genetic causes of CPHD, mutations of genes coding for speci fic or non-specific transcription factors involved in the pituitary ontogenetic development have been implicated, which can result in either non-syndromic CPHD (e.g. mutations of PROP1, POU1F1) or syndromic CPHD in association with ocular defects, midline brain abnormalities or other features (e.g. mutations of HESX1, LHX4)[2, 3]. Almost * Katica Bajuk Studen katica.bajuk@kclj.si 1 Department of Nuclear Medicine, University Medical Centre Ljubljana, Zaloška 7, 1000 Ljubljana, Slovenia 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 Supplementary information The online version of this article (https:// doi.org/10.1007/s12020-019-01949-2) contains supplementary material, which is available to authorized users. 1234567890();,: 1234567890();,: