{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:09:29Z","timestamp":1789016969953,"version":"build-2803163510"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      FHH2 is the rarest subtype of familial hypocalciuric hypercalcemia disorders affecting the CaSR signaling pathway. It is caused by heterozygous loss-of-function mutations in the\n                      <jats:italic>GNA11<\/jats:italic>\n                      gene, encoding G\u03b111 protein. Only seven\n                      <jats:italic>GNA11<\/jats:italic>\n                      pathogenic variants have been reported so far.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case description<\/jats:title>\n                    <jats:p>\n                      We report the case of a 39-year-old man referred to our outpatient clinic for a non-toxic multinodular goiter. During biochemical examination, mild hypercalcemia with normal PTH levels and low urinary calcium excretion (calcium\u2013creatinine clearance ratio&amp;lt; 0.01) was detected. He had no evidence of kidney stones or nephrocalcinosis and demonstrated normal bone mineral density at dual-energy X-ray absorptiometry. A similar biochemical profile in his mother suggested FHH. Following total thyroidectomy for the goiter, the patient\u2019s calcium and PTH levels normalized. Genetic testing identified a novel heterozygous germline frameshift variant in\n                      <jats:italic>GNA11<\/jats:italic>\n                      (c.980_981del, p.His327LeufsTer150) in the proband, his mother, and his 15-month-old normocalcemic daughter. This frameshift variant, which affects the critical GTPase domain, results in a pathogenic elongated protein with 116 additional amino acids, significantly altering its structure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this report, we describe the eighth FHH2 kindred and highlight the biochemical heterogeneity of this rare condition. Our findings demonstrate that the normalization of serum calcium during follow-up does not necessarily exclude the diagnosis. Furthermore, we underscore the clinical importance of integrating genetic findings with longitudinal biochemical data.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1876004","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:28:55Z","timestamp":1789014535000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case report: A Newly Identified G-protein Subunit \u03b1-11 Loss-of-Function Variant Causing Familial Hypocalciuric Hypercalcemia Type 2 in an Italian Kindred"],"prefix":"10.3389","volume":"17","author":[{"given":"Filomena","family":"Cetani","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa","place":["Pisa, Italy"]},{"name":"Endocrine Unit, University Hospital of Pisa","place":["Pisa, 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