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dc.contributor.author Dusatkova P
dc.contributor.author Pfaffle R
dc.contributor.author Brown MR
dc.contributor.author Akulevich N
dc.contributor.author Arnhold IJ
dc.contributor.author Kalina MA
dc.contributor.author Kot K
dc.contributor.author Krzisnik C
dc.contributor.author Lemos MC
dc.contributor.author Malikova J
dc.contributor.author Navardauskaite R
dc.contributor.author Obermannova B
dc.contributor.author Pribilincova Z
dc.contributor.author Sallai, Ágnes
dc.contributor.author Stipancic G
dc.contributor.author Verkauskiene R
dc.contributor.author Cinek O
dc.contributor.author Blum WF
dc.contributor.author Parks JS
dc.contributor.author Austerlitz F
dc.contributor.author Lebl J
dc.date.accessioned 2017-01-23T08:42:03Z
dc.date.available 2017-01-23T08:42:03Z
dc.date.issued 2016
dc.identifier 84930846980
dc.identifier.citation pagination=415-420; journalVolume=24; journalIssueNumber=3; journalTitle=EUROPEAN JOURNAL OF HUMAN GENETICS;
dc.identifier.uri http://repo.lib.semmelweis.hu//handle/123456789/2850
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
dc.date.updated 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


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