title: Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes.
abstract: Pituitary development depends on a complex cascade of interacting transcription factors and signaling molecules. Lesions in this cascade lead to isolated or combined pituitary hormone deficiency (CPHD). The aim of this study was to identify copy number variants (CNVs) in genes known to cause CPHD and to determine their structure. We analyzed 70 CPHD patients from 64 families. Deletions were found in three Turkish families and one family from northern Iraq. In one family we identified a 4.96 kb deletion that comprises the first two exons of POU1F1. In three families a homozygous 15.9 kb deletion including complete PROP1 was discovered. Breakpoints map within highly homologous AluY sequences. Haplotype analysis revealed a shared haplotype of 350 kb among PROP1 deletion carriers. For the first time we were able to assign the boundaries of a previously reported PROP1 deletion. This gross deletion shows strong evidence to originate from a common ancestor in patients with Kurdish descent. No CNVs within LHX3, LHX4, HESX1, GH1 and GHRHR were found. Our data prove multiplex ligation-dependent probe amplification to be a valuable tool for the detection of CNVs as cause of pituitary insufficiencies and should be considered as an analytical method particularly in Kurdish patients.
authors.affiliation: Hospital for Children and Adolescents, Division of Pediatric Endocrinology, University of Leipzig, Leipzig, Germany.
authors.forename: Eleonore
authors.identifier: http://orcid.org/0000-0002-6122-6762
authors.initials: E
authors.lastname: Bertko
authors.affiliation: Hospital for Children and Adolescents, Division of Pediatric Endocrinology, University of Leipzig, Leipzig, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Klammt
authors.affiliation: 2nd Faculty of Medicine, Department of Pediatrics, Charles University in Prague and University Hospital Motol, Prague, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Dusatkova
authors.affiliation: Department of Endocrinology, Ataturk Training and Research Hospital, Izmir, Turkey.
authors.forename: Mithat
authors.initials: M
authors.lastname: Bahceci
authors.affiliation: Hacettepe University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Ankara, Turkey.
authors.forename: Nazli
authors.initials: N
authors.lastname: Gonc
authors.affiliation: Reinier de Graaf Gasthuis, Delft, The Netherlands.
authors.forename: Louise
authors.initials: L
authors.lastname: Ten Have
authors.affiliation: Hacettepe University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Ankara, Turkey.
authors.forename: Nurgun
authors.initials: N
authors.lastname: Kandemir
authors.affiliation: PAN Institute for Endocrinology and Reproductive Medicine, Cologne, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Mansmann
authors.affiliation: 2nd Faculty of Medicine, Department of Pediatrics, Charles University in Prague and University Hospital Motol, Prague, Czech Republic.
authors.forename: Barbora
authors.initials: B
authors.lastname: Obermannova
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Wilma
authors.initials: W
authors.lastname: Oostdijk
authors.affiliation: Hospital for Children and Adolescents, Division of Pediatric Endocrinology, University of Leipzig, Leipzig, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Pfäffle
authors.affiliation: Hospital for Children and Adolescents, Division of Pediatric Endocrinology, University of Leipzig, Leipzig, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Rockstroh-Lippold
authors.affiliation: Hospital for Children and Adolescents, Division of Pediatric Endocrinology, University of Leipzig, Leipzig, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Schlicke
authors.affiliation: Department of Endocrinology, Dicle University, Diyarbakir, Turkey.
authors.forename: Alpaslan Kemal
authors.initials: AK
authors.lastname: Tuzcu
authors.affiliation: Hospital for Children and Adolescents, Division of Pediatric Endocrinology, University of Leipzig, Leipzig, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Pfäffle
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006239:Haplotypes; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007018:Hypopituitarism / Q000235:genetics*; D008297:Male; D010375:Pedigree; D017384:Sequence Deletion; D050817:Transcription Factor Pit-1 / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C494187:POU1F1 protein, human; C102134:Prophet of Pit-1 protein; D050817:Transcription Factor Pit-1