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Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes
E. Bertko, J. Klammt, P. Dusatkova, M. Bahceci, N. Gonc, L. Ten Have, N. Kandemir, G. Mansmann, B. Obermannova, W. Oostdijk, H. Pfäffle, D. Rockstroh-Lippold, M. Schlicke, AK. Tuzcu, R. Pfäffle,
Language English Country England, Great Britain
Document type Case Reports, Journal Article
Grant support
NV16-31211A
MZ0
CEP Register
Digital library NLK
Full text - Article
NLK
Free Medical Journals
from 1977
ProQuest Central
from 2000-01-01 to 2017-12-31
Health & Medicine (ProQuest)
from 2000-01-01 to 2017-12-31
PubMed
28356564
DOI
10.1038/jhg.2017.34
Knihovny.cz E-resources
- MeSH
- Child MeSH
- Adult MeSH
- Haplotypes * MeSH
- Homeodomain Proteins genetics MeSH
- Hypopituitarism genetics MeSH
- Humans MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Pedigree MeSH
- Sequence Deletion * MeSH
- Transcription Factor Pit-1 genetics MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
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.
Department of Endocrinology Ataturk Training and Research Hospital Izmir Turkey
Department of Endocrinology Dicle University Diyarbakir Turkey
Department of Pediatrics Leiden University Medical Center Leiden The Netherlands
PAN Institute for Endocrinology and Reproductive Medicine Cologne Germany
References provided by Crossref.org
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- $a 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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