Show simple item record Dusatkova P Pfaffle R Brown MR Akulevich N Arnhold IJ Kalina MA Kot K Krzisnik C Lemos MC Malikova J Navardauskaite R Obermannova B Pribilincova Z Sallai, Ágnes Stipancic G Verkauskiene R Cinek O Blum WF Parks JS Austerlitz F Lebl J 2017-01-23T08:42:03Z 2017-01-23T08:42:03Z 2016
dc.identifier 84930846980
dc.identifier.citation pagination=415-420; journalVolume=24; journalIssueNumber=3; journalTitle=EUROPEAN JOURNAL OF HUMAN GENETICS;
dc.identifier.uri doi:10.1038/ejhg.2015.126
dc.description.abstract Two variants (c.[301_302delAG];[301_302delAG] and c.[150delA];[150delA]) in the PROP1 gene are the most common genetic causes of recessively inherited combined pituitary hormones deficiency (CPHD). Our objective was to analyze in detail the origin of the two most prevalent variants. In the multicentric study were included 237 patients with CPHD and their 15 relatives carrying c.[301_302delAG];[301_302delAG] or c.[150delA];[150delA] or c.[301_302delAG];[ 150delA]. They originated from 21 different countries worldwide. We genotyped 21 single-nucleotide variant markers flanking the 9.6-Mb region around the PROP1 gene that are not in mutual linkage disequilibrium in the general populations - a finding of a common haplotype would be indicative of ancestral origin of the variant. Haplotypes were reconstructed by Phase and Haploview software, and the variant age was estimated using an allelic association method. We demonstrated the ancestral origin of both variants - c.[301_302delAG] was carried on 0.2 Mb-long haplotype in a majority of European patients arising ~101 generations ago (confidence interval 90.1-116.4). Patients from the Iberian Peninsula displayed a different haplotype, which was estimated to have emerged 23.3 (20.1-29.1) generations ago. Subsequently, the data indicated that both the haplotypes were transmitted to Latin American patients ~13.8 (12.2-17.0) and 16.4 (14.4-20.1) generations ago, respectively. The c.[150delA] variant that was carried on a haplotype spanning about 0.3 Mb was estimated to appear 43.7 (38.4-52.7) generations ago. We present strong evidence that the most frequent variants in the PROP1 gene are not a consequence of variant hot spots as previously assumed, but are founder variants.European Journal of Human Genetics advance online publication, 10 June 2015; doi:10.1038/ejhg.2015.126.
dc.relation.ispartof urn:issn:1018-4813
dc.title Genesis of two most prevalent PROP1 gene variants causing combined pituitary hormone deficiency in 21 populations
dc.type Journal Article 2015-11-27T13:05:06Z
dc.language.rfc3066 en
dc.identifier.mtmt 2929740
dc.identifier.pubmed 26059845
dc.contributor.department SE/AOK/K/II. Sz. Gyermekgyógyászati Klinika
dc.contributor.institution Semmelweis Egyetem

Files in this item



This item appears in the following Collection(s)

Show simple item record

Search DSpace

Advanced Search


My Account