{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:48Z","timestamp":1787028528358,"version":"build-2736575974"},"reference-count":13,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,9]],"date-time":"2023-12-09T00:00:00Z","timestamp":1702080000000},"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>Serum phosphate concentration is regulated by renal phosphate reabsorption and mediated by sodium\u2013phosphate cotransporters. Germline mutations in genes encoding these cotransporters have been associated with clinical phenotypes, variably characterized by hyperphosphaturia, hypophosphatemia, recurrent kidney stones, skeletal demineralization, and early onset osteoporosis. We reported a 33-year-old male patient presenting a history of recurrent nephrolithiasis and early onset osteopenia in the lumbar spine and femur. He was tested, through next generation sequencing (NGS), by using a customized multigenic panel containing 33 genes, whose mutations are known to be responsible for the development of congenital parathyroid diseases. Two further genes, SLC34A1 and SLC34A3, encoding two sodium\u2013phosphate cotransporters, were additionally tested. A novel germline heterozygous mutation was identified in the SLC34A1 gene, c.1627G&gt;T (p.Gly543Cys), currently not reported in databases of human gene mutations and scientific literature. SLC34A1 germline heterozygous mutations have been associated with the autosomal dominant hypophosphatemic nephrolithiasis\/osteoporosis type 1 (NPHLOP1). Consistently, alongside the clinical features of NPHLOP1, our patient experienced recurrent nephrolithiasis and lumbar and femoral osteopenia at a young age. Genetic screening for the p.Gly453Cys variant and the clinical characterization of his first-degree relatives associated the presence of the variant in one younger brother, presenting renal colic and microlithiasis, suggesting p.Gly453Cys is possibly associated with renal altered function in the NPHLOP1 phenotype.<\/jats:p>","DOI":"10.3390\/ijms242417289","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T03:25:31Z","timestamp":1702265131000},"page":"17289","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Novel Heterozygous Mutation c.1627G&gt;T (p.Gly543Cys) in the SLC34A1 Gene in a Male Patient with Recurrent Nephrolithiasis and Early Onset Osteopenia: A Case Report"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8576-9606","authenticated-orcid":false,"given":"Francesca","family":"Giusti","sequence":"first","affiliation":[{"name":"Donatello Bone Clinic, Villa Donatello Hospital, 50019 Sesto Fiorentino, Italy"},{"name":"Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3678-4922","authenticated-orcid":false,"given":"Francesca","family":"Marini","sequence":"additional","affiliation":[{"name":"Fondazione FIRMO Onlus, Italian Foundation for the Research on Bone Diseases, 50129 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9036-7903","authenticated-orcid":false,"given":"Hatim","family":"Al-alwani","sequence":"additional","affiliation":[{"name":"Divisions of Endocrinology and Metabolism and Geriatrics, McMaster University, Hamilton, ON L8S 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Marasco","sequence":"additional","affiliation":[{"name":"Personal Genomics SRL, 37136 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Garagnani","sequence":"additional","affiliation":[{"name":"Personal Genomics SRL, 37136 Verona, Italy"},{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy"},{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliya A.","family":"Khan","sequence":"additional","affiliation":[{"name":"Divisions of Endocrinology and Metabolism and Geriatrics, McMaster University, Hamilton, ON L8S 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8741-0592","authenticated-orcid":false,"given":"Maria Luisa","family":"Brandi","sequence":"additional","affiliation":[{"name":"Donatello Bone Clinic, Villa Donatello Hospital, 50019 Sesto Fiorentino, Italy"},{"name":"Fondazione FIRMO Onlus, Italian Foundation for the Research on Bone Diseases, 50129 Florence, Italy"},{"name":"IRCCS San Raffaele Hospital, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1007\/s00467-012-2175-z","article-title":"Phosphate homeostasis and its role in bone health","volume":"27","author":"Penido","year":"2012","journal-title":"Pediatr. Nephrol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e13715","DOI":"10.14814\/phy2.13715","article-title":"Clinical, biochemical, and pathophysiological analysis of SLC34A1 mutations","volume":"6","author":"Fearn","year":"2018","journal-title":"Physiol. Rep."},{"key":"ref_3","first-page":"S145","article-title":"Phosphate transport in the kidney","volume":"23","author":"Murer","year":"2010","journal-title":"J. Nephrol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.mam.2012.07.007","article-title":"Phosphate transporters of the SLC20 and SLC34 families","volume":"34","author":"Forster","year":"2013","journal-title":"Mol. Asp. Med."},{"key":"ref_5","first-page":"983","article-title":"Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter","volume":"347","author":"Huart","year":"2012","journal-title":"N. Eng. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1086\/499409","article-title":"SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis","volume":"78","author":"Bergwitz","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1086\/499410","article-title":"Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3","volume":"78","author":"Eckstein","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5372","DOI":"10.1073\/pnas.95.9.5372","article-title":"Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities","volume":"95","author":"Beck","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1359\/jbmr.2003.18.12.2135","article-title":"Functional characterization of two naturally occurring mutations in the human sodium-phosphate cotransporter type IIa","volume":"18","author":"Virkki","year":"2003","journal-title":"J. Bone Miner. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1681\/ASN.2014101025","article-title":"Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia","volume":"27","author":"Schlingmann","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e15617","DOI":"10.1097\/MD.0000000000015617","article-title":"A novel heterozygous mutation c.680A>G (p. N227S) in SLC34A1 gene leading to autosomal dominant hypophosphatemia: A case report","volume":"98","author":"Chen","year":"2019","journal-title":"Medicine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"300060519896146","DOI":"10.1177\/0300060519896146","article-title":"Heterozygous mutation of SLC34A1 in patients with hypophosphatemic kidney stones and osteoporosis: A case report","volume":"48","author":"Ma","year":"2020","journal-title":"J. Int. Med. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/24\/17289\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:35:55Z","timestamp":1760132155000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/24\/17289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,9]]},"references-count":13,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["ijms242417289"],"URL":"https:\/\/doi.org\/10.3390\/ijms242417289","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,9]]}}}