{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T11:55:01Z","timestamp":1777895701062,"version":"3.51.4"},"reference-count":30,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01NS107733-25"],"award-info":[{"award-number":["1R01NS107733-25"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Rhizomelic chondrodysplasia punctata type 1 (RCDP1) is a peroxisomal disorder characterized by skeletal shortening, intellectual disability, seizures, cataracts, and reduced lifespans. RCDP1 is caused by biallelic loss-of-function variants in PEX7, which encodes a protein required for importing select enzymes into the peroxisome matrix, including those essential for ether lipid synthesis (e.g., plasmalogens) and the branched-chain fatty acid catabolism. Plasmalogen deficiency is a hallmark of RCDP1 and other peroxisomal disorders, including RCDP types 2-5 (RCDP2-5) and Zellweger spectrum disorders (ZSD). Here, we performed comprehensive metabolomic profiling of clinical samples from RCDP patients and Pex7-deficient mouse models. We identified profound neurometabolic disturbances in the cerebral cortex and cerebellum of Pex7-deficient mice involving multiple lipid classes, including phosphatidylethanolamines (PEs), phosphatidylcholines (PCs), acylcarnitines, and sphingomyelins. Notably, many of these neurometabolic alterations were absent in patient and Pex7-deficient mouse plasma, indicating that plasma-based profiling can underrepresent the extent of CNS lipid remodeling. Overall, these findings reveal novel insights into neurometabolic adaptations to plasmalogen deficiency and suggest the potential involvement of additional pathways that may contribute to neurological dysfunction in RCDP.<\/jats:p>","DOI":"10.3390\/biom16010006","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T11:03:46Z","timestamp":1766142226000},"page":"6","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolomic Profiling Reveals Brain Lipid Alterations in PEX7-Deficient Models of Rhizomelic Chondrodysplasia Punctata"],"prefix":"10.3390","volume":"16","author":[{"given":"Riya","family":"Sankhe","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA"},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital (TCH), Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3985-4495","authenticated-orcid":false,"given":"Meredith I.","family":"Williams","sequence":"additional","affiliation":[{"name":"Development, Disease Models and Therapeutics Graduate Program, Baylor College of Medicine (BCM), Houston, TX 77030, USA"},{"name":"Center for Precision Environmental Health, Baylor College of Medicine (BCM), Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wedad","family":"Fallatah","sequence":"additional","affiliation":[{"name":"Genetics Laboratories, Department of Genetic Medicine, Kennedy Krieger Institute, Johns Hopkins University, Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1189-3102","authenticated-orcid":false,"given":"Laura","family":"Mackay","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Layne","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Plant and Wildlife Sciences, Brigham Young University, Provo, UT 84604, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1982-5996","authenticated-orcid":false,"given":"Pranjali","family":"Bhagwat","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah H.","family":"Elsea","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA"},{"name":"BCM Human Genome Sequencing Center, Baylor College of Medicine (BCM), Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1621-5164","authenticated-orcid":false,"given":"Nancy","family":"Braverman","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Human Genetics, McGill University and the Research Institute of the McGill University Health Center, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5245-5910","authenticated-orcid":false,"given":"Michael F.","family":"Wangler","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA"},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital (TCH), Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1152\/physrev.00051.2021","article-title":"The Physiological Functions of Human Peroxisomes","volume":"103","author":"Wanders","year":"2023","journal-title":"Physiol. 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