{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T03:29:52Z","timestamp":1747193392818,"version":"3.40.5"},"reference-count":0,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cytogenet Genome Res"],"published-print":{"date-parts":[[2017]]},"abstract":"<jats:p>Germline intragenic mutations in the&lt;i&gt; GNAS &lt;\/i&gt;locus result in pseudohypoparathyroidism type 1a (PHP1a) and related conditions. Nearly half of the previously reported &lt;i&gt;GNAS&lt;\/i&gt; intragenic mutations were structural variants, including 3 tandem duplications of 12-25 bp. However, the precise mutation spectrum and the genomic basis of &lt;i&gt;GNAS&lt;\/i&gt; structural variants remain to be clarified. Here, we report a de novo 50-bp tandem duplication in&lt;i&gt; GNAS&lt;\/i&gt; (c.723_772dup50, p.Glu259Leufs*29) identified in a patient with typical clinical features of PHP1a. The mutant transcript was predicted to undergo mRNA decay or encode a nonfunctional protein. The 2 breakpoints of the duplication shared a 1-bp microhomology but were not associated with long homology or nucleotide stretches. We also examined the breakpoint structures of 3 previously reported &lt;i&gt;GNAS&lt;\/i&gt; duplications and found that 1 had a structure similar to that of our case, while the remaining 2 had blunt-ended breakpoints without microhomologies. In silico analyses revealed that the &lt;i&gt;GNAS&lt;\/i&gt;-flanking region was not enriched with repeats, palindromes, noncanonical DNA motifs, or GC content. This study expands the mutation spectrum of &lt;i&gt;GNAS&lt;\/i&gt; and provides the first indication that &lt;i&gt;GNAS&lt;\/i&gt; intragenic structural variants are induced by multiple processes, including nonhomologous end-joining and\/or microhomology-mediated break-induced replication, independently of known rearrangement-inducing DNA features.<\/jats:p>","DOI":"10.1159\/000485644","type":"journal-article","created":{"date-parts":[[2018,1,10]],"date-time":"2018-01-10T22:01:37Z","timestamp":1515621697000},"page":"125-130","source":"Crossref","is-referenced-by-count":1,"title":["A de novo 50-bp &lt;b&gt;&lt;i&gt;GNAS&lt;\/i&gt;&lt;\/b&gt; Intragenic Duplication in a Patient with Pseudohypoparathyroidism Type 1a"],"prefix":"10.1159","volume":"153","author":[{"given":"Erina","family":"Suzuki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryosuke","family":"Bo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaori","family":"Sue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Awano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsutomu","family":"Ogata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Narumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayo","family":"Kagami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichiro","family":"Sano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9971-4035","authenticated-orcid":false,"given":"Maki","family":"Fukami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2018,1,11]]},"container-title":["Cytogenetic and Genome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/485644","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/485644","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:26:47Z","timestamp":1745425607000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000485644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017]]},"references-count":0,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,2,28]]}},"URL":"https:\/\/doi.org\/10.1159\/000485644","archive":["Portico"],"relation":{},"ISSN":["1424-8581","1424-859X"],"issn-type":[{"type":"print","value":"1424-8581"},{"type":"electronic","value":"1424-859X"}],"subject":[],"published":{"date-parts":[[2017]]}}}