Altered Cerebrospinal Fluid Proteins in Smith–Lemli–Opitz Syndrome
Smith–Lemli–Opitz Syndrome (SLOS) is a rare, autosomal recessive, neurocognitive disorder caused by pathological variants in the 7-dehydrocholesterol reductase gene (<i>DHCR7</i>), leading to impaired cholesterol biosynthesis. The biochemical results of these defects include the accumula...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , , , , , , , , , |
| منشور في: |
2025
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| الموضوعات: | |
| الوسوم: |
إضافة وسم
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| الملخص: | Smith–Lemli–Opitz Syndrome (SLOS) is a rare, autosomal recessive, neurocognitive disorder caused by pathological variants in the 7-dehydrocholesterol reductase gene (<i>DHCR7</i>), leading to impaired cholesterol biosynthesis. The biochemical results of these defects include the accumulation of the cholesterol precursor, 7-dehydrocholesterol (7-DHC), and typically reduced cholesterol. Individuals with SLOS present with a spectrum of developmental anomalies and neurocognitive impairments. Despite various therapeutic approaches being explored, there is no curative treatment, highlighting the need for reliable biomarkers to better understand the disease’s pathophysiology, allowing for important therapeutic intervention studies. Here, we utilized discovery-based mass spectrometry to perform quantitative proteomic profiling of cerebrospinal fluid (CSF) from SLOS individuals compared to unaffected controls. Our analyses identified several differentially expressed proteins that could serve as potential biomarkers for assessing therapeutic efficacy and advancing our understanding of SLOS. Notably, we observed previously unrecognized alterations in the reelin signaling pathway and a decrease in dopamine excretion, implicating these processes in the development and progression of the SLOS. |
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