New insights of altered lipid profile in Fragile X Syndrome
Open accessAbstract
BACKGROUND: Fragile X Syndrome (FXS) is the main genetic cause of autism and intellectual deficiency resulting the absence of the Fragile X Mental Retardation Protein (FMRP). Clinical picture is characterized by cognitive impairment associated with a broad spectrum of psychiatric comorbidities including autism spectrum disorders and attention-deficit/hyperactivity disorders. Some of these disorders have been associated with lipid abnormalities and lower cholesterol levels. Since lipids are important for neuronal development, we aim to investigate the lipid profile of French Canadian-FXS individuals and to identify the altered components of cholesterol metabolism as well as their association with clinical profile. METHODS: Anthropometric data were collected from 25 FXS individuals and 26 controls. Lipid assessment included: total cholesterol (TC), triglycerides, LDL, HDL, ApoB, ApoA1, PCSK9, Lp(a) and lipoprotein electrophoresis. Aberrant and adaptive behaviour of affected individuals was respectively assessed by the ABC-C and ABAS questionnaires. RESULTS: FXS participants had a higher body mass index as compared to controls while 38% of them had TC<10th percentile. Lower levels of LDL, HDL and apoA1 were observed in FXS group as compared to controls. However, PCSK9 levels did not differ between the two groups. As expected, PCSK9 levels correlated with total cholesterol (rs = 0.61, p = 0.001) and LDL (rs = 0.46, p = 0.014) in the control group, while no association was present in the FXS group. An inverse relationship was observed between total cholesterol and aberrant behaviour as determined by ABC-C total score. CONCLUSION: Our results showed the presence of hypocholesterolemia in French Canadian-FXS population, a condition that seems to influence their clinical phenotype. We identified for the first time a potential underlying alteration of PCSK9 function in FXS that could result from the absence of FMRP. Further investigations are warranted to better understand the association between cholesterol metabolism, PCSK9, FMRP and clinical profile.
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Statistically significant lower levels of total cholesterol and HDL-cholesterol have been observed in the serum of FXS patients compared to the normal population.
“statistically significant lower levels of total cholesterol and HDL-cholesterol have been observed in the serum of FXS patients if compared to the normal population [26,27].”
From Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome (2022) · cites this paper as [27]
The Results (Lipid profile) report significantly lower total cholesterol (p<0.001) and HDL-C (p=0.002) in male FXS participants than in the age-adjusted normal male population. The analysis was not pursued for female participants, so the unqualified claim about FXS patients is broader than the finding reported here. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIndividuals with fragile X syndrome have low cholesterol, HDL, LDL, and ApoA1 levels, and their degree of maladaptive behaviors occurs in inverse relationship to cholesterol levels.
“Individuals with fragile X syndrome have low cholesterol, HDL, LDL, and ApoA1 levels [39–41], and their degree of maladaptive behaviors occurs in inverse relationship to cholesterol levels [40].”
From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [40]
PCSK9 has abnormal function in individuals with fragile X syndrome.
“For example, PCSK9 is important in regulation of lipoproteins and neuronal apoptosis [101] and has abnormal function in individuals with fragile X syndrome [40, 97].”
From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [40]
The Fmr1-Δexon 8 rat model mimics the reduced plasma cholesterol content observed in FXS patients.
“Our study demonstrates that the Fmr1-Δexon 8 preclinical model mimics the reduced plasma cholesterol content observed in FXS patients [26,27].”
From Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome (2022) · cites this paper as [27]
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References 19 · Cited by 36
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- Authors
- Çaku, A., Seidah, N. G., Lortie, A., Gagné, N., Perron, P., Dubé, J., & Corbin, F.
- Affiliations
- Université de Sherbrooke (CA)
- Montreal Clinical Research Institute (CA)
- Corresponding author
- Çaku, Artuela
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-03-23
- Volume
- 12
- Issue
- 3
- Pages
- e0174301
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5363930
- OpenAlex
- W2599157542
- Cited by
- 36
- References
- 19
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 7 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 1 · 2017: 1
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Foundation of Stars
- Diabetes, Obesity, and Cardiovascular Complications
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- fragile X syndrome, lipid profile, hypocholesterolemia, FMRP, PCSK9, cholesterol metabolism, LDL cholesterol, HDL cholesterol, apolipoprotein A-I, aberrant behaviour, autism spectrum disorder, intellectual disability, body mass index
- MeSH terms
- Proprotein Convertase 9, Apolipoproteins B, Cholesterol, Female, Fragile X Syndrome, Humans, Lipids, Cholesterol, HDL, Cholesterol, LDL, Male, Triglycerides, Body Mass Index, Case-Control Studies, Apolipoprotein A-I, Lipid Metabolism, Young Adult
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