DHCR24-related desmosterolosis in the first reported Turkish patient: Expanding the genotypic and phenotypic spectrum
Journal of Clinical Lipidology, cilt.20, sa.2, ss.451-456, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 20 Sayı: 2
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.jacl.2025.10.078
- Dergi Adı: Journal of Clinical Lipidology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CINAHL, EMBASE, MEDLINE
- Sayfa Sayıları: ss.451-456
- Anahtar Kelimeler: 3-beta-hydroxysterol delta-24-reductase (DHCR24), 3D Protein modeling, Cholesterol biosynthesis, Desmosterol, Sterol
- Çanakkale Onsekiz Mart Üniversitesi Adresli: Evet
Özet
BACKGROUND Desmosterolosis is a ultra-rare autosomal recessive disorder caused by biallelic variants in the DHCR24 gene, which encodes 3-beta-hydroxysterol delta-24-reductase—an enzyme involved in the final step of cholesterol biosynthesis. Here, we report a 3.5-year-old female with previously unreported compound heterozygous DHCR24 variants: c.1412A>G (p.Tyr471Cys), and c.275C>T (p.Thr92Met). CASE PRESENTATION The patient presented with agenesis of the corpus callosum, hypotonia, developmental delay, and dysmorphic facial features. METHOD AND RESULTS Trio-clinical exome sequencing confirmed the trans configuration of the variants. Plasma desmosterol levels were elevated >50-fold (134 ng/L; reference ≤2.5 ng/L), supporting the diagnosis. In silico 3D protein modeling demonstrated structural alterations associated with both variants. CONCLUSION A review of reported cases revealed consistent findings of corpus callosum agenesis, developmental delay, and ocular abnormalities. Our case contributes to the limited body of literature on DHCR24 -related desmosterolosis and expands the variant spectrum, emphasizing the importance of integrating clinical, biochemical, and computational approaches in diagnosing rare metabolic disorders.