{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:41:48Z","timestamp":1791092508333,"version":"4.1.0"},"reference-count":42,"publisher":"BMJ","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2010,8,18]]},"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Pseudohypoparathyroidism type Ib (PHP-Ib) is due to epigenetic changes at the imprinted <jats:italic>GNAS<\/jats:italic> locus, including loss of methylation at the A\/B differentially methylated region (DMR) and sometimes at the XL and AS DMRs and gain of methylation at the NESP DMR.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To investigate if quantitative measurement of the methylation at the <jats:italic>GNAS<\/jats:italic> DMRs identifies subtypes of PHP-Ib.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design and methods<\/jats:title>\n                  <jats:p>In 19 patients with PHP-Ib and 7 controls, methylation was characterised at the four <jats:italic>GNAS<\/jats:italic> DMRs through combined bisulfite restriction analysis and quantified through cytosine specific real-time PCR in blood lymphocyte DNA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A principal component analysis using the per cent of methylation at seven cytosines of the <jats:italic>GNAS<\/jats:italic> locus provided three clusters of subjects (controls n=7, autosomal dominant PHP-Ib with loss of methylation restricted to the A\/B DMR n=3, and sporadic PHP-Ib with broad <jats:italic>GNAS<\/jats:italic> methylation changes n=16) that matched perfectly the combined bisulfite restriction analysis classification. Furthermore, three sub-clusters of patients with sporadic PHP-Ib, that displayed different patterns of methylation, were identified: incomplete changes at all DMRs compatible with somatic mosaicism (n=5), profound epigenetic changes at all DMRs (n=8), and unmodified methylation at XL in contrast with the other DMRs (n=3). Interestingly, parathyroid hormone concentration at the time of diagnosis correlated with the per cent of methylation at the A\/B DMR.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Quantitative assessment of the methylation in blood lymphocyte DNA is of clinical relevance, allows the diagnosis of PHP-Ib, and identifies subtypes of PHP-Ib. These epigenetic findings suggest mosaicism at least in some patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2010.081356","type":"journal-article","created":{"date-parts":[[2010,10,23]],"date-time":"2010-10-23T20:25:24Z","timestamp":1287865524000},"page":"55-63","source":"Crossref","is-referenced-by-count":52,"title":["Quantification of the methylation at the <i>GNAS<\/i> locus identifies subtypes of sporadic pseudohypoparathyroidism type 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