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In\n                    <jats:italic>Npc1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice, Rapamycin, an autophagy inductor, yielded opposite results depending on genetic background, suggesting the presence of pharmacogenomic modifiers. To identify them, we used a genotyped yeast panel designed for gene mapping and the NPC\u2010mimetic U18666A (U18\u2010drug) in the presence and absence of rapamycin. We evaluated cell growth, vacuolar fragmentation, and transcriptomics across diverse strains. Linkage analysis based on cell growth identified a significant locus, leading to the prioritization of nine genes. Notably,\n                    <jats:italic>ccs1<\/jats:italic>\n                    (copper chaperone for superoxide dismutase) and\n                    <jats:italic>avo2<\/jats:italic>\n                    (TORC2 subunit) deletions decreased cell growth compared to U18\u2010Rapa in WT cells, while\n                    <jats:italic>irc21<\/jats:italic>\n                    (DNA damage and ceramide metabolism) increased it. Our results suggest that genomic variants within these genes should be assessed before using rapamycin for NPC. This study represents a crucial step towards personalized rapamycin therapeutics.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70214","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T08:28:12Z","timestamp":1781771292000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Rapamycin Pharmacogenomic Approach for the Childhood Dementia\n                    <scp>N<\/scp>\n                    iemann\u2010\n                    <scp>P<\/scp>\n                    ick C"],"prefix":"10.1002","volume":"49","author":[{"given":"Benjam\u00edn","family":"Szenfeld","sequence":"first","affiliation":[{"name":"Centro de Gen\u00e9tica y Gen\u00f3mica, Facultad de Medicina Cl\u00ednica Alemana Universidad del Desarrollo  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Macarena","family":"Las Heras","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica y Gen\u00f3mica, Facultad de Medicina Cl\u00ednica Alemana Universidad del Desarrollo  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Rubilar","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica y Gen\u00f3mica, Facultad de Medicina Cl\u00ednica Alemana Universidad del Desarrollo  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2254-0417","authenticated-orcid":false,"given":"Pablo","family":"Villarreal","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00f3mica y Bioinform\u00e1tica, Facultad de Ciencias, Ingenier\u00eda y Tecnolog\u00eda Universidad Mayor  Santiago Chile"},{"name":"Millennium Institute for Integrative Biology (iBio)  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Olgu\u00edn","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica y Gen\u00f3mica, Facultad de Medicina Cl\u00ednica Alemana Universidad del Desarrollo  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3022-469X","authenticated-orcid":false,"given":"Francisco A.","family":"Cubillos","sequence":"additional","affiliation":[{"name":"Millennium Institute for Integrative Biology (iBio)  Santiago Chile"},{"name":"Departamento de Biolog\u00eda, Facultad de Qu\u00edmica y Biolog\u00eda Universidad de Santiago de Chile  Santiago Chile"},{"name":"Millenium Nucleus of Patagonian Limit of Life (LiLi)  Valdivia Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9951-2174","authenticated-orcid":false,"given":"Andr\u00e9s D.","family":"Klein","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica y Gen\u00f3mica, Facultad de Medicina Cl\u00ednica Alemana Universidad del Desarrollo  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"issue":"1","key":"e_1_2_12_2_1","first-page":"166","article-title":"The Unique Case of the Niemann\u2010Pick Type C Cholesterol Storage Disorder","volume":"12","author":"Klein A. 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