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Case Report

Genome sequencing identifies uniparental isodisomy of chromosome 2p and a homozygous ABCG5 variant, enabling effective treatment of pediatric hypercholesterolemia after 13 years of therapeutic resistance: A case report

  • Authors:
    • Hannah Kassaie
    • Chanatjit Cheawsamoot
    • Sunisa Kanchanasutthiyakorn
    • Kanokwan Santawong
    • Sirinuch Chomtho
    • Rungroj Thangpong
    • Vorasuk Shotelersuk
  • View Affiliations / Copyright

    Affiliations: Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand, Center of Excellence in Pediatric Nutrition, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
  • Article Number: 178
    |
    Published online on: September 17, 2025
       https://doi.org/10.3892/br.2025.2056
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Abstract

Sitosterolemia is a rare inherited disorder caused by mutations in ABCG5 or ABCG8 genes, resulting in abnormal accumulation of phytosterols. Clinically, it often resembles familial hypercholesterolemia (FH), which is much more common. The present study described the first reported case of sitosterolemia caused by paternal segmental uniparental isodisomy of chromosome 2p, leading to a homozygous pathogenic variant in ABCG5. The patient developed xanthomas at age two and was initially misdiagnosed with FH. Despite statin therapy and a cholesterol‑restricted diet, the LDL cholesterol of the patient remained elevated, and the patient experienced intermittent knee periarthritis. At age 15, genome sequencing revealed sitosterolemia. After introducing dietary phytosterol restriction and ezetimibe, the lipid levels of the patient normalized within 4 months, with marked clinical improvement. The present case highlights the importance of genetic testing in patients with treatment‑resistant hyperlipidemia and represents the first reported instance of sitosterolemia caused by uniparental disomy.
View Figures

Figure 1

Images of the clinical manifestations
of the patient. (A) Tendinous xanthomas on both Achilles tendons (2
years old). (B) Tendinous xanthomas on right Achilles tendon and
ankle (2 years old). (C) Tendinous xanthoma on right toe knuckle (2
years old). (D) Tendinous xanthomas and inflammation of right knee
(periarthritis) (13 years old). (E) Tendinous xanthomas and
inflammation of left knee (periarthritis) (13 years old).

Figure 2

TrioMix tool displays the VAF for SNPs
on each chromosome, separated by maternal and paternal
contributions. In Group A SNPs (where only SNPs that are homozygous
in either parent are considered), the maternal allele frequency
plot for SNPs on the short arm of chromosome 2 revealed a value of
~0, while the paternal plot registered at ~1. This indicates that
the patient inherited parental homozygous SNPs on the p arm of
chromosome 2 solely from the father. In Group B SNPs (where only
SNPs that are heterozygous in either parent are considered), the
VAF of SNPs on the p arm of chromosome 2 exhibits a maternal allele
frequency of 0, coupled with a paternal plot showing allele
frequencies predominantly at 0 and 1, with an absence of
heterozygous SNPs (0.5) along the p arm. This pattern suggests
paternal uniparental isodisomy of most of the p arm of chromosome
2, wherein the patient inherited two identical copies of this
chromosomal segment from the father, with no contribution from the
mother. VAF, variant allele frequencies; SNPs, single nucleotide
polymorphisms.

Figure 3

Chemical structures of cholesterol and
three common phytosterols. The structural differences between each
plant sterol and cholesterol are circled in red.
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Copy and paste a formatted citation
Spandidos Publications style
Kassaie H, Cheawsamoot C, Kanchanasutthiyakorn S, Santawong K, Chomtho S, Thangpong R and Shotelersuk V: Genome sequencing identifies uniparental isodisomy of chromosome 2p and a homozygous <em>ABCG5</em> variant, enabling effective treatment of pediatric hypercholesterolemia after 13 years of therapeutic resistance: A case report. Biomed Rep 23: 178, 2025.
APA
Kassaie, H., Cheawsamoot, C., Kanchanasutthiyakorn, S., Santawong, K., Chomtho, S., Thangpong, R., & Shotelersuk, V. (2025). Genome sequencing identifies uniparental isodisomy of chromosome 2p and a homozygous <em>ABCG5</em> variant, enabling effective treatment of pediatric hypercholesterolemia after 13 years of therapeutic resistance: A case report. Biomedical Reports, 23, 178. https://doi.org/10.3892/br.2025.2056
MLA
Kassaie, H., Cheawsamoot, C., Kanchanasutthiyakorn, S., Santawong, K., Chomtho, S., Thangpong, R., Shotelersuk, V."Genome sequencing identifies uniparental isodisomy of chromosome 2p and a homozygous <em>ABCG5</em> variant, enabling effective treatment of pediatric hypercholesterolemia after 13 years of therapeutic resistance: A case report". Biomedical Reports 23.5 (2025): 178.
Chicago
Kassaie, H., Cheawsamoot, C., Kanchanasutthiyakorn, S., Santawong, K., Chomtho, S., Thangpong, R., Shotelersuk, V."Genome sequencing identifies uniparental isodisomy of chromosome 2p and a homozygous <em>ABCG5</em> variant, enabling effective treatment of pediatric hypercholesterolemia after 13 years of therapeutic resistance: A case report". Biomedical Reports 23, no. 5 (2025): 178. https://doi.org/10.3892/br.2025.2056
Copy and paste a formatted citation
x
Spandidos Publications style
Kassaie H, Cheawsamoot C, Kanchanasutthiyakorn S, Santawong K, Chomtho S, Thangpong R and Shotelersuk V: Genome sequencing identifies uniparental isodisomy of chromosome 2p and a homozygous <em>ABCG5</em> variant, enabling effective treatment of pediatric hypercholesterolemia after 13 years of therapeutic resistance: A case report. Biomed Rep 23: 178, 2025.
APA
Kassaie, H., Cheawsamoot, C., Kanchanasutthiyakorn, S., Santawong, K., Chomtho, S., Thangpong, R., & Shotelersuk, V. (2025). Genome sequencing identifies uniparental isodisomy of chromosome 2p and a homozygous <em>ABCG5</em> variant, enabling effective treatment of pediatric hypercholesterolemia after 13 years of therapeutic resistance: A case report. Biomedical Reports, 23, 178. https://doi.org/10.3892/br.2025.2056
MLA
Kassaie, H., Cheawsamoot, C., Kanchanasutthiyakorn, S., Santawong, K., Chomtho, S., Thangpong, R., Shotelersuk, V."Genome sequencing identifies uniparental isodisomy of chromosome 2p and a homozygous <em>ABCG5</em> variant, enabling effective treatment of pediatric hypercholesterolemia after 13 years of therapeutic resistance: A case report". Biomedical Reports 23.5 (2025): 178.
Chicago
Kassaie, H., Cheawsamoot, C., Kanchanasutthiyakorn, S., Santawong, K., Chomtho, S., Thangpong, R., Shotelersuk, V."Genome sequencing identifies uniparental isodisomy of chromosome 2p and a homozygous <em>ABCG5</em> variant, enabling effective treatment of pediatric hypercholesterolemia after 13 years of therapeutic resistance: A case report". Biomedical Reports 23, no. 5 (2025): 178. https://doi.org/10.3892/br.2025.2056
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