{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T06:44:59Z","timestamp":1757313899984,"version":"3.40.5"},"reference-count":10,"publisher":"Walter de Gruyter GmbH","issue":"0","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n To contribute a novel sonic hedgehog (SHH) gene variant in association with a novel-meagerly described phenotype and discuss SHH signaling pathway pathology.<\/jats:p>\n <\/jats:sec>\n \n Case presentation<\/jats:title>\n We present a 5-year-old boy with excessive hyponatremia and natriuresis, microform holoprosencephaly and microsomia, with morphologically intact hypothalamic\u2013pituitary\u2013adrenal (HPA) axis, and hypoaldosteronism, yet without hyperreninemia, hyperkalemia, dehydration episodes, or glucocorticoid insufficiency. Extensive workup excluded common causes of salt-wasting and revealed a novel variant of unknown significance on the sonic hedgehog (SHH) gene; NM_000193.4:c.755_757del (p.Phe252del), in heterozygosity.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Salt-wasting in children is predominantly caused by central nervous system lesions, renal tubular dysfunction, or adrenal insufficiency. The SHH protein is a signaling molecule, essential in embryogenesis-including HPA axis differentiation. Inactivating SHH variants disrupt the signaling pathway, leading to dysplasia or dysfunction of target organs. What\u2019s new: \u2022 We analyze the patient's phenotype in the light of this novel variant \u2022 Patient\u2019s isolated aldosterone deficiency possibly implies a selective signaling defect affecting the development of adrenal zona glomerulosa \u2022 Unexplained hyporeninemia and hypokalemia in the context of hypoaldosteronism raise questions on SHH signaling pathophysiology.<\/jats:p>\n <\/jats:sec>","DOI":"10.1515\/jpem-2023-0015","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T04:20:36Z","timestamp":1682482836000},"source":"Crossref","is-referenced-by-count":1,"title":["Novel sonic hedgehog gene variant in a patient with hyponatremia, microsomia, and midline defects; phenotype description in association with a variant of unknown significance [c.755_757del p.(Phe252del)] and an approach to salt-wasting in SHH-related adrenal disorders"],"prefix":"10.1515","volume":"0","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5629-9916","authenticated-orcid":false,"given":"Marita","family":"Antoniadi","sequence":"first","affiliation":[{"name":"Pediatric Department , Penteli Children\u2019s Hospital , Athens , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitra Irinna","family":"Vitoratou","sequence":"additional","affiliation":[{"name":"Pediatric Department , Penteli Children\u2019s Hospital , Athens , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Marinou","sequence":"additional","affiliation":[{"name":"Pediatric Department , Penteli Children\u2019s Hospital , Athens , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Fafoula","sequence":"additional","affiliation":[{"name":"Pediatric Department , Penteli Children\u2019s Hospital , Athens , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fani","family":"Mylona","sequence":"additional","affiliation":[{"name":"Pediatric Department , Penteli Children\u2019s Hospital , Athens , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danai","family":"Palaiologou","sequence":"additional","affiliation":[{"name":"Genesis Genoma Lab, Genetic Diagnosis, Clinical Genetics & Research , Athens , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lazaros","family":"Leandros","sequence":"additional","affiliation":[{"name":"Genesis Genoma Lab, Genetic Diagnosis, Clinical Genetics & Research , Athens , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stavroula","family":"Kostaridou","sequence":"additional","affiliation":[{"name":"Pediatric Department , Penteli Children\u2019s Hospital , Athens , Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2023,4,27]]},"reference":[{"doi-asserted-by":"crossref","unstructured":"Bizzarri, C, Olivini, N, Pedicelli, S, Marini, R, Giannone, G, Cambiaso, P, et al.. Congenital primary adrenal insufficiency and selective aldosterone defects presenting as salt-wasting in infancy: a single center 10-year experience. Ital J Pediatr 2016;42:73. https:\/\/doi.org\/10.1186\/s13052-016-0282-3.","key":"2023042604203153715_j_jpem-2023-0015_ref_001","DOI":"10.1186\/s13052-016-0282-3"},{"doi-asserted-by":"crossref","unstructured":"Richards, S, Aziz, N, Bale, S, Bick, D, Das, S, Gastier-Foster, J, et al.. 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. Genet Med 2015;17:405\u201324. https:\/\/doi.org\/10.1038\/gim.2015.30.","key":"2023042604203153715_j_jpem-2023-0015_ref_002","DOI":"10.1038\/gim.2015.30"},{"doi-asserted-by":"crossref","unstructured":"Sasai, N, Toriyama, M, Kondo, T. Hedgehog signal and genetic disorders. 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