{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:43:57Z","timestamp":1789447437086,"version":"build-2803163510"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:sec><jats:title>Context<\/jats:title><jats:p>Pseudohypoparathyroidism type Ib (PHP-Ib) is a rare disorder resulting from genetic and epigenetic aberrations in the <jats:italic>GNAS<\/jats:italic> complex. PHP-Ib, usually defined by renal resistance to parathyroid hormone, is due to a maternal loss of <jats:italic>GNAS<\/jats:italic> exon A\/B methylation and leads to decreased expression of the stimulatory G protein \u03b1 (Gs\u03b1) in specific tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To clarify the usefulness of methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), we evaluated genetic and epigenetic changes of the <jats:italic>GNAS<\/jats:italic> locus in Japanese PHP-Ib patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Retrospective case series.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>We studied 13 subjects with PHP-Ib (three families with eight affected members and one unaffected member and four sporadic cases).<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements<\/jats:title><jats:p>The methylation status of <jats:italic>GNAS<\/jats:italic> differentially methylated regions (DMRs) was evaluated using MS-MLPA. The main outcome measure was the presence of deletion mutations in the <jats:italic>GNAS<\/jats:italic> locus and <jats:italic>STX16<\/jats:italic>, which were assessed using MLPA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In all familial PHP-Ib cases, a \u223c3\u200akb deletion of <jats:italic>STX16<\/jats:italic> and demethylation of the A\/B domain were identified. In contrast, no deletion was detected throughout the entire <jats:italic>GNAS<\/jats:italic> locus region in the sporadic cases. Broad methylation abnormalities were observed in the <jats:italic>GNAS<\/jats:italic> DMRs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>MS-MLPA allows for precise and rapid analysis of the methylation status in <jats:italic>GNAS<\/jats:italic> DMRs as well as the detection of microdeletion mutations in PHP-Ib. Results confirm the previous findings in this disorder and demonstrate that this method is valuable for the genetic evaluation and visualizing the methylation status. The MS-MLPA assay is a useful tool that may facilitate making the molecular diagnosis of PHP-Ib.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-12-0548","type":"journal-article","created":{"date-parts":[[2012,11,7]],"date-time":"2012-11-07T06:46:09Z","timestamp":1352270769000},"page":"169-175","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":10,"title":["Genetic and epigenetic states of the GNAS complex in pseudohypoparathyroidism type Ib using methylation-specific multiplex ligation-dependent probe amplification assay"],"prefix":"10.1093","volume":"168","author":[{"given":"Akiko","family":"Yuno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Usui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Yambe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiichiro","family":"Higashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ugi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junji","family":"Shinoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Mashio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Shimatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"issue":"10","key":"1_40428768","doi-asserted-by":"publisher","first-page":"3020","DOI":"10.1210\/jc.2011-1048","volume":"96","year":"2011","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"2","key":"2_18787052","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1159\/000083895","volume":"63","author":"Bastepe","year":"2005","journal-title":"Hormone research","ISSN":"https:\/\/id.crossref.org\/issn\/0301-0163","issn-type":"print"},{"issue":"10","key":"3_42810932","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1055\/s-0032-1304232","volume":"44","author":"Mantovani","year":"2012","journal-title":"Hormone and metabolic research. 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