Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes

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 an...

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Autores principales: Bertko, Eleonore, Klammt, Jürgen, Dusatkova, Petra, Bahceci, Mithat, Gonc, Nazli, ten Have, Louise, Kandemir, Nurgun, Mansmann, Georg, Obermannova, Barbora, Oostdijk, Wilma, Pfäffle, Heike, Rockstroh-Lippold, Denise, Schlicke, Marina, Tuzcu, Alpaslan Kemal, Pfäffle, Roland
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5537413/
https://www.ncbi.nlm.nih.gov/pubmed/28356564
http://dx.doi.org/10.1038/jhg.2017.34
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author Bertko, Eleonore
Klammt, Jürgen
Dusatkova, Petra
Bahceci, Mithat
Gonc, Nazli
ten Have, Louise
Kandemir, Nurgun
Mansmann, Georg
Obermannova, Barbora
Oostdijk, Wilma
Pfäffle, Heike
Rockstroh-Lippold, Denise
Schlicke, Marina
Tuzcu, Alpaslan Kemal
Pfäffle, Roland
author_facet Bertko, Eleonore
Klammt, Jürgen
Dusatkova, Petra
Bahceci, Mithat
Gonc, Nazli
ten Have, Louise
Kandemir, Nurgun
Mansmann, Georg
Obermannova, Barbora
Oostdijk, Wilma
Pfäffle, Heike
Rockstroh-Lippold, Denise
Schlicke, Marina
Tuzcu, Alpaslan Kemal
Pfäffle, Roland
author_sort Bertko, Eleonore
collection PubMed
description 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.
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spelling pubmed-55374132017-08-07 Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes Bertko, Eleonore Klammt, Jürgen Dusatkova, Petra Bahceci, Mithat Gonc, Nazli ten Have, Louise Kandemir, Nurgun Mansmann, Georg Obermannova, Barbora Oostdijk, Wilma Pfäffle, Heike Rockstroh-Lippold, Denise Schlicke, Marina Tuzcu, Alpaslan Kemal Pfäffle, Roland J Hum Genet Original Article 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. Nature Publishing Group 2017-08 2017-03-30 /pmc/articles/PMC5537413/ /pubmed/28356564 http://dx.doi.org/10.1038/jhg.2017.34 Text en Copyright © 2017 The Japan Society of Human Genetics
spellingShingle Original Article
Bertko, Eleonore
Klammt, Jürgen
Dusatkova, Petra
Bahceci, Mithat
Gonc, Nazli
ten Have, Louise
Kandemir, Nurgun
Mansmann, Georg
Obermannova, Barbora
Oostdijk, Wilma
Pfäffle, Heike
Rockstroh-Lippold, Denise
Schlicke, Marina
Tuzcu, Alpaslan Kemal
Pfäffle, Roland
Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes
title Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes
title_full Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes
title_fullStr Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes
title_full_unstemmed Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes
title_short Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes
title_sort combined pituitary hormone deficiency due to gross deletions in the pou1f1 (pit-1) and prop1 genes
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5537413/
https://www.ncbi.nlm.nih.gov/pubmed/28356564
http://dx.doi.org/10.1038/jhg.2017.34
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