Article
Biology
Hideaki Tomita, Kelly M. Hines, Josi M. Herron, Amy Li, David W. Baggett, Libin Xu
Summary: Deficient DHCR7 in SLOS leads to cholesterol deficiency and accumulation of 7-DHC. This study reveals that loss of DHCR7 causes accumulation of 7-DHC-derived oxysterol metabolites, premature neurogenesis, and depletion of cortical precursor pool. The major oxysterol, DHCEO, mediates these effects through crosstalk between GR and TrkB.
Article
Biotechnology & Applied Microbiology
A. Rozdzynska-Swiatkowska, E. Ciara, P. Halat-Wolska, M. Krajewska-Walasek, A. Jezela-Stanek
Summary: Smith-Lemli-Opitz syndrome (SLOS) is a disorder caused by a defect in cholesterol biosynthesis, with physical manifestations including growth restriction and microcephaly. Studies analyzing the correlation between genotype, biochemical markers, and growth parameters in individuals with SLOS are currently lacking.
JOURNAL OF APPLIED GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Babunageswararao Kanuri, Vincent Fong, Sithara Raju Ponny, Keri A. Tallman, Sriganesh Ramachandra Rao, Ned Porter, Steven J. Fliesler, Shailendra B. Patel
Summary: Researchers have generated a conditional Dhcr7 knockout mouse model with liver-specific deletion, which demonstrated minimal impact on sterol metabolism in the liver. This model provides a valuable tool for further exploration of the pathophysiology of SLOS through temporal, cell and tissue-specific loss of DHCR7.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Cell Biology
Bethany A. Freel, Benjamin A. Kelvington, Sonali Sengupta, Malini Mukherjee, Kevin R. Francis
Summary: Cholesterol homeostasis is critical to neurodevelopment, and disruption of cholesterol biosynthesis can lead to neurological deficits. Astrocyte immune activation is a hallmark pathology in many diseases, but the impact of DHCR7 on astrocyte function and immune activation is still unclear. The study found that astrocytes from Dhcr7 mutant mice display immune reactive characteristics and the interaction with microglia may contribute to the neurological phenotypes observed in disorders of cholesterol biosynthesis.
DISEASE MODELS & MECHANISMS
(2022)
Article
Genetics & Heredity
Jong Eun Park, Taeheon Lee, Kyeongsu Ha, Chang-Seok Ki
Summary: This study analyzed carrier frequencies of SLOS in East Asians and Koreans using exome data from the Genome Aggregation Database (gnomAD), and found that East Asians had a lower carrier frequency (0.4%) compared to other ethnicities (1-3%), while Koreans had a similar or lower carrier frequency (1.0%). The variant spectrums of DHCR7 in East Asian and Korean populations differed greatly from those of other ethnic groups.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Chemistry, Medicinal
Dario Ghersi, Thiago C. Genaro-Mattos
Summary: Research indicates that certain medications inhibit a key enzyme in the cholesterol biosynthesis pathway, with shared chemical structures among these drugs. By employing a computational approach, enriched fragments within these medications can be identified to better understand their inhibitory mechanisms.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2022)
Article
Chemistry, Analytical
Jan Klouda, Lenka Benesova, Pavel Kocovsky, Karolina Schwarzova-Peckova
Summary: 7-Dehydrocholesterol is an essential biomarker for Smith-Lemli-Opitz syndrome, and its electrochemical oxidation allows for voltammetric determination, providing clinical value for diagnosis and monitoring. This study establishes a reliable method for diagnosing SLOS and monitoring the biotransformation of 7-dehydrocholesterol to cholecalciferol.
Article
Pediatrics
Peter A. Kaub, Peter C. Sharp, Enzo Ranieri, Janice M. Fletcher
Summary: Studies have shown a high incidence of autistic spectrum features in individuals with SLOS, but it is not appropriate to use ASD as the sole clinical indication for biochemical testing for SLOS based on historical test data analysis.
JOURNAL OF PAEDIATRICS AND CHILD HEALTH
(2022)
Article
Genetics & Heredity
N. Begic, Z. Begic, E. Begic
Summary: This paper presents a patient with Smith-Lemli-Opitz syndrome (SLOS) and discusses the diagnosis and treatment modalities. The patient, a 6-year-old girl, exhibits global developmental retardation, lack of motor development, and enhanced muscle tone. She is currently under the care of various specialists including pediatric neurologists, gastroenterologists, nephrologists, and cardiologists.
BALKAN JOURNAL OF MEDICAL GENETICS
(2021)
Article
Chemistry, Multidisciplinary
Thiago C. Genaro-Mattos, Allison Anderson, Luke B. Allen, Zeljka Korade, Karoly Mirnics
Summary: The research has shown that Dhcr7 single-allele mutations can affect the metabolism of ARI and CAR, leading to increased turnover of ARI and CAR in tissues from Dhcr7(+/-) animals, partially due to higher levels of Cyp2d6. Additionally, lower drug levels were found in DHCR7(+/-) heterozygous cells.
Article
Chemistry, Analytical
Yitao Luo, Zhengyuan Liu, Yujie Zeng, Yuxiao Zhang, Yujing Luan, Li Ma, Li Chen, Lin Zou, Jingmin Yang, Zhibin Huang, Yulan Rao, Chengqiang Zhang
Summary: This study developed a gas chromatography-mass spectrometry based method for simultaneous detection of 7-dehydrocholesterol and cholesterol in human plasma, providing a useful tool for the diagnosis, treatment, and research of Smith-Lemli-Opitz syndrome.
JOURNAL OF SEPARATION SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Katalin Koczok, Laszlo Horvath, Zeljka Korade, Zoltan Andras Mezei, Gabriella P. Szabo, Ned A. Porter, Eszter Kovacs, Karoly Mirnics, Istvan Balogh
Summary: The study investigated the effects of vitamin E supplementation in SLOS patients, showing a reduction in certain behavioral issues and an increase in plasma vitamin E concentration. The clinical response to therapy was associated with the baseline 7-DHC and 8-DHC/cholesterol ratio in some patients.
Article
Biochemistry & Molecular Biology
Jonas Abdel-Khalik, Thomas Hearn, Alison L. Dickson, Peter J. Crick, Eylan Yutuc, Karl Austin-Muttitt, Brian W. Bigger, Andrew A. Morris, Cedric H. Shackleton, Peter T. Clayton, Takashi Iida, Ria Sircar, Rajat Rohatgi, Hanns-Ulrich Marschall, Jan Sjovall, Ingemar Bjorkhem, Jonathan G. L. Mullins, William J. Griffiths, Yuqin Wang
Summary: A newly identified pathway of bile acid biosynthesis in patients with SLOS and pregnancy, involving intermediates that modulate the activity of Smo, an oncoprotein that mediates Hedgehog signaling, may be responsible for some features of SLOS.
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Ernst J. Schaefer, G. Stephen Tint, P. Barton Duell, Robert D. Steiner
Summary: These disorders, including cerebrotendinous xanthomatosis (CTX), sitosterolemia, and Smith-Lemli Opitz syndrome (SLOS), are rare inborn errors of metabolism with various clinical manifestations. Early diagnosis and appropriate treatment are crucial for managing the progression and complications of these disorders. Collaboration between healthcare professionals is essential in providing comprehensive care for patients with these rare metabolic conditions.
JOURNAL OF CLINICAL LIPIDOLOGY
(2021)
Article
Medicine, General & Internal
Simone Coupe, Ashley Hertzog, Carolyn Foran, Adviye Ayper Tolun, Megan Suthern, Clara W. T. Chung, Carolyn Ellaway
Summary: Smith-Lemli-Opitz syndrome (SLOS) is a common genetic cause of developmental delay, often accompanied by 2,3 toe syndactyly. This case series highlights a milder phenotype of SLOS, characterized by neurocognitive impairments and the presence of 2,3 toe syndactyly.
CLINICAL CASE REPORTS
(2023)