{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T12:39:26Z","timestamp":1785155966400,"version":"3.55.0"},"reference-count":28,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T00:00:00Z","timestamp":1728518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Defects of the GNAS gene have been mainly associated with pseudohypoparathyroidism Ia. To date, pathogenic missense, frameshift, non-sense and splicing variants have been described in all the 13 exons of the GNAS gene. Of them, a specific mutation, namely the 4 bp deletion c.565_568delGACT, is currently considered a mutation hotspot. Recent articles performed genotype\u2013phenotype correlations in patients with GNAS-related pseudohypoparathyroidism Ia (PHP1a) but a specific focus on this hotspot is still lacking. We reported two cases, from our department, of PHP1a associated with c.565_568delGACT deletion and performed a literature review of all the previously reported cases of the 4 bp deletion hotspot. We found a higher prevalence of brachydactyly, round face, intellectual disability and subcutaneous\/heterotopic ossifications in patients with the c.565_568delGACT as compared to the other variants in the GNAS gene. The present study highlights the different prevalence of some clinical features in patients with the c.565_568delGACT variant in the GNAS gene, suggesting the possibility of a personalized diagnostic follow-up and surveillance for these patients.<\/jats:p>","DOI":"10.3390\/ijms252010913","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T11:34:36Z","timestamp":1728560076000},"page":"10913","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genotype\u2013Phenotype Correlation of GNAS Gene: Review and Disease Management of a Hotspot Mutation"],"prefix":"10.3390","volume":"25","author":[{"given":"Lorenzo","family":"Cipriano","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Ferrigno","sequence":"additional","affiliation":[{"name":"Endocrinology and Auxology Unit, Pediatrics Speciality Department, A.O.R.N. Santobono-Pausilipon, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Immacolata","family":"Andolfo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3624-7721","authenticated-orcid":false,"given":"Roberta","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Cioffi","sequence":"additional","affiliation":[{"name":"Endocrinology and Auxology Unit, Pediatrics Speciality Department, A.O.R.N. Santobono-Pausilipon, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Savanelli","sequence":"additional","affiliation":[{"name":"Endocrinology and Auxology Unit, Pediatrics Speciality Department, A.O.R.N. Santobono-Pausilipon, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Pellino","sequence":"additional","affiliation":[{"name":"Endocrinology and Auxology Unit, Pediatrics Speciality Department, A.O.R.N. Santobono-Pausilipon, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Klain","sequence":"additional","affiliation":[{"name":"Endocrinology and Auxology Unit, Pediatrics Speciality Department, A.O.R.N. 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