{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T13:34:21Z","timestamp":1763559261185,"version":"3.45.0"},"reference-count":21,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Nephrocalcinosis, characterized by the deposition of calcium salts within the renal parenchyma, is frequently identified incidentally in pediatric patients and may be associated with underlying genetic disorders. Sotos syndrome, a rare congenital overgrowth condition associated with neurodevelopment delay and congenital defects caused by mutations or deletions in the NSD1 gene, has been sporadically linked to renal abnormalities, including nephrocalcinosis. Clinical presentation: We report a case of a male patient with Sotos syndrome and concurrent nephrocalcinosis, in whom genetic analysis revealed a microdeletion of chromosome 5q35 with a 2.2 Mb deletion encompassing both NSD1 and SLC34A1 genes. The SLC34A1 gene encodes the NaPi-IIa sodium\u2013phosphate cotransporter, essential for phosphate reabsorption in the renal proximal tubule. Haploinsufficiency of SLC34A1 is implicated in dysregulated phosphate and calcium homeostasis, predisposing to hypercalciuria and nephrocalcinosis. Longitudinal follow-up demonstrated biochemical stability, resolution of nephrocalcinosis, and preserved renal function, supporting the hypothesis of an age-dependent attenuation in NaPi-IIa function. Conclusions: This case underscores the relevance of contiguous gene deletions in shaping complex clinical phenotypes and highlights the importance of early wide clinical screening in patients with Sotos syndrome to mitigate long-term renal complications.<\/jats:p>","DOI":"10.3390\/jcm14228200","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T12:55:31Z","timestamp":1763556931000},"page":"8200","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nephrocalcinosis in a Child with Sotos Syndrome: A Case Report of Contiguous Gene Syndrome Encompassing NSD1 and SLC34A1 Genes"],"prefix":"10.3390","volume":"14","author":[{"given":"Agnieszka","family":"Bargenda-Lange","sequence":"first","affiliation":[{"name":"Department and Clinic of Pediatric Nephrology, Wroclaw Medical University (UMW), 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Jakubowska","sequence":"additional","affiliation":[{"name":"Department and Clinic of Pediatric Nephrology, Wroclaw Medical University (UMW), 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Medy\u0144ska","sequence":"additional","affiliation":[{"name":"Department and Clinic of Pediatric Nephrology, Wroclaw Medical University (UMW), 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Bajtek","sequence":"additional","affiliation":[{"name":"Department and Clinic of Pediatrics, Endocrinology, Diabetology and Metabolic Diseases, Wroclaw Medical University (UMW), 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2930-9549","authenticated-orcid":false,"given":"Robert","family":"\u015amigiel","sequence":"additional","affiliation":[{"name":"Department and Clinic of Pediatrics, Endocrinology, Diabetology and Metabolic Diseases, Wroclaw Medical University (UMW), 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Kili\u015b-Pstrusi\u0144ska","sequence":"additional","affiliation":[{"name":"Department and Clinic of Pediatric Nephrology, Wroclaw Medical University (UMW), 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1007\/s00467-023-05879-0","article-title":"Genetic testing in children with nephrolithiasis and nephrocalcinosis","volume":"38","author":"Gefen","year":"2023","journal-title":"Pediatr. Nephrol."},{"key":"ref_2","first-page":"2","article-title":"Sotos syndrome","volume":"7","author":"Baujat","year":"2007","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_3","first-page":"2050","article-title":"Normal Reference Values","volume":"Volume 2","author":"Emma","year":"2022","journal-title":"Pediatric Nephrology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1093\/clinchem\/40.11.2099","article-title":"Congenital adrenal hypoplasia, Duchenne muscular dystrophy, and glycerol kinase deficiency: Importance of laboratory investigations in delineating a contiguous gene deletion syndrome","volume":"40","author":"Cole","year":"1994","journal-title":"Clin. Chem."},{"key":"ref_5","first-page":"717","article-title":"New Bacterial Artificial Chromosome and Commercial FISH Probes for the 22q11.2 Region in Patients with Congenital Heart Defect and with Phenotype Resembling DiGeorge and Velocardiofacial Syndromes","volume":"16","author":"Piotrowicz","year":"2007","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1023\/A:1005660826652","article-title":"Isolated and contiguous glycerol kinase gene disorders: A review","volume":"23","author":"Sjarif","year":"2000","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1373\/clinchem.2006.072397","article-title":"A multiplex assay for the detection and mapping of complex glycerol kinase deficiency","volume":"52","author":"Klein","year":"2006","journal-title":"Clin. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/sj.ejhg.5201172","article-title":"Glycerol kinase deficiency: Residual activity explained by reduced transcription and enzyme conformation","volume":"12","author":"Sjarif","year":"2004","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S1096-7192(03)00094-5","article-title":"Clinical heterogeneity and molecular findings in five Polish patients with glycerol kinase deficiency: Investigation of two splice site mutations with computerized splice junction analysis and Xp21 gene-specific mRNA analysis","volume":"79","author":"Hellerud","year":"2003","journal-title":"Mol. Genet. Metab."},{"key":"ref_10","first-page":"e67800","article-title":"Progressive Polycystic Kidney Disease in an Infant Girl With TSC2\/PKD1 Contiguous Gene Syndrome","volume":"16","author":"Hashimoto","year":"2024","journal-title":"Cureus"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1038\/ki.2008.485","article-title":"Characterization of large rearrangements in autosomal dominant polycystic kidney disease and the PKD1\/TSC2 contiguous gene syndrome","volume":"74","author":"Consugar","year":"2008","journal-title":"Kidney Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1136\/jmg.35.4.273","article-title":"Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis: A new X linked contiguous gene deletion syndrome?","volume":"35","author":"Jonsson","year":"1998","journal-title":"Med. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00467-017-3873-3","article-title":"Renal phosphate handling and inherited disorders of phosphate reabsorption: An update","volume":"34","author":"Wagner","year":"2019","journal-title":"Pediatr. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s13023-024-03135-8","article-title":"Biallelic and monoallelic pathogenic variants in CYP24A1 and SLC34A1 genes cause idiopathic infantile hypercalcemia","volume":"19","author":"Wang","year":"2024","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1056\/NEJMoa020028","article-title":"Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter","volume":"347","author":"Huart","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"64","DOI":"10.6065\/apem.2019.24.1.64","article-title":"Infantile hypercalcemia with novel compound heterozygous mutation in SLC34A1 encoding renal sodium-phosphate cotransporter 2a: A case report","volume":"24","author":"Kang","year":"2019","journal-title":"Ann. Pediatr. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1002\/humu.20568","article-title":"Heterogeneity of NSD1 alterations in 116 patients with Sotos syndrome","volume":"28","author":"Bonnet","year":"2007","journal-title":"Hum. Mutat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1007\/s00467-011-1884-z","article-title":"Sotos syndrome, infantile hypercalcemia, and nephrocalcinosis: A contiguous gene syndrome","volume":"26","author":"Kenny","year":"2011","journal-title":"Pediatr. Nephrol."},{"key":"ref_19","first-page":"219","article-title":"Sotos Syndrome and Nephrocalcinosis a Rare But Possible Association Due to Impact on Contiguous Genes","volume":"17","year":"2025","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1093\/ndt\/gfaa178","article-title":"Long-term outcome of the survivors of infantile hypercalcaemia with CYP24A1 and SLC34A1 mutations","volume":"36","author":"Janiec","year":"2021","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.kint.2024.08.035","article-title":"Presentation and outcome in carriers of pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter NPT 2a and 2c","volume":"107","author":"Brunkhorst","year":"2025","journal-title":"Kidney Int."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/22\/8200\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T13:30:00Z","timestamp":1763559000000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/22\/8200"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,19]]},"references-count":21,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["jcm14228200"],"URL":"https:\/\/doi.org\/10.3390\/jcm14228200","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,19]]}}}