{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:53:48Z","timestamp":1760151228143,"version":"build-2065373602"},"reference-count":73,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["EC08\/00236"],"award-info":[{"award-number":["EC08\/00236"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenetic hereditary renal disease, promoting end-stage renal disease (ESRD). Klinefelter syndrome (KS) is a consequence of an extra copy of the X chromosome in males. Main symptoms in KS include hypogonadism, tall stature, azoospermia, and a risk of cardiovascular diseases, among others. Gitelman syndrome (GS) is an autosomal recessive disorder caused by SLC12A3 variants, and is associated with hypokalemia, hypomagnesemia, hypocalciuria, normal or low blood pressure, and salt loss. The three disorders have distinct and well-delineated clinical, biochemical, and genetic findings. We here report a male patient with ADPKD who developed early chronic renal failure leading to ESRD, presenting with an intracranial aneurysm and infertility. NGS identified two de novo PKD1 variants, one known (likely pathogenic), and a previously unreported variant of uncertain significance, together with two SLC12A3 pathogenic variants. In addition, cytogenetic analysis showed a 47, XXY karyotype. We investigated the putative impact of this rare association by analyzing possible clinical, biochemical, and\/or genetic interactions and by comparing the evolution of renal size and function in the proband with three age-matched ADPKD (by variants in PKD1) cohorts. We hypothesize that the coexistence of these three genetic disorders may act as modifiers with possible synergistic actions that could lead, in our patient, to a rapid ADPKD progression.<\/jats:p>","DOI":"10.3390\/genes13030394","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T22:35:09Z","timestamp":1645569309000},"page":"394","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rapidly Progressing to ESRD in an Individual with Coexisting ADPKD and Masked Klinefelter and Gitelman Syndromes"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9170-8746","authenticated-orcid":false,"given":"Ram\u00f3n","family":"Peces","sequence":"first","affiliation":[{"name":"Servicio de Nefrolog\u00eda, Hospital Universitario La Paz, IdiPAZ, Universidad Aut\u00f3noma, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Peces","sequence":"additional","affiliation":[{"name":"Area de Tecnolog\u00eda de la Informaci\u00f3n, SESCAM, 45071 Toledo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roc\u00edo","family":"Mena","sequence":"additional","affiliation":[{"name":"Instituto de Gen\u00e9tica M\u00e9dica y Molecular (INGEMM), Hospital Universitario La Paz, IdiPAZ, Universidad Aut\u00f3noma, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilio","family":"Cuesta","sequence":"additional","affiliation":[{"name":"Servicio de Radiolog\u00eda, Hospital Universitario La Paz, IdiPAZ, Universidad Aut\u00f3noma, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2393-7800","authenticated-orcid":false,"given":"Fe Amalia","family":"Garc\u00eda-Santiago","sequence":"additional","affiliation":[{"name":"Instituto de Gen\u00e9tica M\u00e9dica y Molecular (INGEMM), Hospital Universitario La Paz, IdiPAZ, Universidad Aut\u00f3noma, 28046 Madrid, Spain"},{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras, ISCIII, 28046 Madrid, Spain"},{"name":"ITHACA, European Reference Network, Hospital Universitario La Paz, IdiPAZ, Universidad Aut\u00f3noma, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Ossorio","sequence":"additional","affiliation":[{"name":"Servicio de Nefrolog\u00eda, Hospital Universitario La Paz, IdiPAZ, Universidad Aut\u00f3noma, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Afonso","sequence":"additional","affiliation":[{"name":"Servicio de Nefrolog\u00eda, Hospital Universitario La Paz, IdiPAZ, Universidad Aut\u00f3noma, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6324-4825","authenticated-orcid":false,"given":"Pablo","family":"Lapunzina","sequence":"additional","affiliation":[{"name":"Instituto de Gen\u00e9tica M\u00e9dica y Molecular (INGEMM), Hospital Universitario La Paz, IdiPAZ, Universidad Aut\u00f3noma, 28046 Madrid, Spain"},{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras, ISCIII, 28046 Madrid, Spain"},{"name":"ITHACA, European Reference Network, Hospital Universitario La Paz, IdiPAZ, Universidad Aut\u00f3noma, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5611-2659","authenticated-orcid":false,"given":"Juli\u00e1n","family":"Nevado","sequence":"additional","affiliation":[{"name":"Instituto de Gen\u00e9tica M\u00e9dica y Molecular (INGEMM), Hospital Universitario La Paz, IdiPAZ, Universidad Aut\u00f3noma, 28046 Madrid, Spain"},{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras, ISCIII, 28046 Madrid, Spain"},{"name":"ITHACA, European Reference Network, Hospital Universitario La Paz, IdiPAZ, Universidad Aut\u00f3noma, 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1681\/ASN.2012070650","article-title":"Type of PKD1 mutation influences renal outcome in ADPKD","volume":"24","author":"Gall","year":"2013","journal-title":"J. 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