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
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
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
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
Genetics & Heredity
Christopher K. Zalewski, Sarah A. Sydlowski, Kelly A. King, Simona Bianconi, An Dang Do, Forbes D. Porter, Carmen C. Brewer
Summary: This study describes the auditory phenotype in patients with SLOS, revealing that 65.6% of patients in the cohort have peripheral or retrocochlear auditory dysfunction, with a heterogeneous audiometric phenotype including conductive, mixed, and sensorineural hearing loss. Additionally, 21.9% of patients show abnormal auditory brainstem responses indicative of retrocochlear dysfunction, requiring objective assessment methods to estimate hearing sensitivity.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
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
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
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
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
Biochemistry & Molecular Biology
Bruce A. Pfeffer, Libin Xu, Steven J. Fliesler
Summary: Transcriptomic analysis on a SLOS animal model revealed up-regulation of pathways such as endoplasmic reticulum stress, oxidative stress, DNA damage and repair, and autophagy in cells treated with oxysterols. The two oxysterols exert their effects through different molecular mechanisms, with changes in expression of key genes confirmed by immunofluorescence confocal microscopy. These findings expand our understanding of retinal degeneration and SLOS pathobiology, identifying potential new druggable targets for therapeutic intervention.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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)
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
Medicine, General & Internal
Elif Ece Eren, Nurbanu Bilgin, Nafiye Urganci, Gulsen Kose
Summary: A 34-day-old patient with hypertrophic pyloric stenosis was suspected to have Smith-Lemli-Opitz syndrome (SLOS) due to clinical and biochemical characteristics. Genomic analysis revealed homozygous mutations in the DHCR7 gene, indicating the genetic basis of the disorder in this patient.
MEDICAL BULLETIN OF SISLI ETFAL HOSPITAL
(2021)
Article
Nutrition & Dietetics
Kara L. Calkins, Andrea DeBarber, Robert D. Steiner, Martiniano J. Flores, Tristan R. Grogan, Susanne M. Henning, Laurie Reyen, Robert S. Venick
JOURNAL OF PARENTERAL AND ENTERAL NUTRITION
(2018)
Article
Biochemistry & Molecular Biology
Jonas Abdel-Khalik, Peter J. Crick, Eylan Yutuc, Andrea E. DeBarber, P. Barton Duell, Robert D. Steiner, Ioanna Laina, Yuqin Wang, William J. Griffiths
Article
Genetics & Heredity
Mahim Jain, Allison Tam, Jay R. Shapiro, Robert D. Steiner, Peter A. Smith, Michael B. Bober, Tracy Hart, David Cuthbertson, Jeff Krischer, Mary Mullins, Sunil Bellur, Peter H. Byers, Melanie Pepin, Michaela Durigova, Francis H. Glorieux, Frank Rauch, Brendan Lee, V. Reid Sutton, Sandesh C. S. Nagamani, David R. Eyre, Deborah Krakow, Laura Tosi, Cathleen L. Raggio, Eric S. Orwoll, Eric T. Rush
GENETICS IN MEDICINE
(2019)
Article
Genetics & Heredity
Allison Tam, Shan Chen, Evan Schauer, Ingo Grafe, Venkata Bandi, Jay R. Shapiro, Robert D. Steiner, Peter A. Smith, Michael B. Bober, Tracy Hart, David Cuthbertson, Jeffrey Krischer, Mary Mullins, Peter H. Byers, Robert A. Sandhaus, Michaela Durigova, Francis H. Glorieux, Frank Rauch, Vernon Reid Sutton, Brendan Lee, Eric T. Rush, Sandesh C. S. Nagamani
Article
Genetics & Heredity
Laura Milko, Birgit H. Funke, Ray E. Hershberger, Danielle R. Azzariti, Kristy Lee, Erin R. Riggs, Edgar A. Rivera-Munoz, Meredith A. Weaver, Annie Niehaus, Erin L. Currey, William J. Craigen, Rong Mao, Kenneth Offit, Robert D. Steiner, Christa L. Martin, Heidi L. Rehm, Michael S. Watson, Erin M. Ramos, Sharon E. Plon, Jonathan S. Berg
GENETICS IN MEDICINE
(2019)
Editorial Material
Genetics & Heredity
Robert D. Steiner
GENETICS IN MEDICINE
(2019)
Article
Genetics & Heredity
Edgar A. Rivera-Munoz, Laura V. Milko, Steven M. Harrison, Danielle R. Azzariti, C. Lisa Kurtz, Kristy Lee, Jessica L. Mester, Meredith A. Weaver, Erin Currey, William Craigen, Charis Eng, Birgit Funke, Madhuri Hegde, Ray E. Hershberger, Rong Mao, Robert D. Steiner, Lisa M. Vincent, Christa L. Martin, Sharon E. Plon, Erin Ramos, Heidi L. Rehm, Michael Watson, Jonathan S. Berg
Article
Pediatrics
Meghan Miller, Erica D. Musser, Gregory S. Young, Brent Olson, Robert D. Steiner, Joel T. Nigg
Article
Genetics & Heredity
Karen M. Kruger, Angela Caudill, Mercedes Rodriguez Celin, Sandesh C. S. Nagamani, Jay R. Shapiro, Robert D. Steiner, Michael B. Bober, Tracy Hart, David Cuthbertson, Jeff Krischer, Peter H. Byers, Michaela Durigova, Francis H. Glorieux, Frank Rauch, V. Reid Sutton, Brendan Lee, Eric T. Rush, Peter A. Smith, Gerald F. Harris
GENETICS IN MEDICINE
(2019)
Article
Pediatrics
Michael P. Whyte, Edward Leung, William R. Wilcox, Johannes Liese, Jesus Argente, Gabriel A. Martos-Moreno, Amy Reeves, Kenji P. Fujita, Scott Moseley, Christine Hofmann, Michael Beck, Linda DiMeglio, Paul Wuh-Liang Hwu, Katherine L. Madson, Upasana Nanda, Peter Simm, Jill Simmons, Joel Steelman, Robert D. Steiner, Andrea Superti-Furga
JOURNAL OF PEDIATRICS
(2019)
Article
Genetics & Heredity
Keren Machol, Trevor D. Hadley, Jake Schmidt, David Cuthbertson, Henri Traboulsi, Rodrigo C. Silva, Chloe Citron, Sobiah Khan, Kate Citron, Erin Carter, Kenneth Brookler, Jay R. Shapiro, Robert D. Steiner, Peter H. Byers, Francis H. Glorieux, Michaela Durigova, Peter Smith, Michael B. Bober, Vernon R. Sutton, Brendan H. Lee, Sandesh C. S. Nagamani, Cathleen Raggio, Jen-Marc Retrouvey, Paul Esposito, Eric Rush, David Eyre, Danielle Gomez, Gerald Harris, Tracy Hart, Mahim Jain, Deborah Krakow, Jeffrey Krischer, Eric Orwoll, Laura Tosi, Frank Rauch
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2020)
Article
Cell Biology
Dimuthu Alankarage, Annabelle Enriquez, Robert D. Steiner, Cathy Raggio, Megan Higgins, Di Milnes, David T. Humphreys, Emma L. Duncan, Duncan B. Sparrow, Philip F. Giampietro, Gavin Chapman, Sally L. Dunwoodie
Summary: This study evaluated the functional impact of the SMAD4-I500V variant, identified in two previously unpublished individuals with Myhre syndrome, and provided new insights into the molecular mechanism of SMAD4-I500V dysfunction. The results showed that SMAD4-I500V had severely compromised transcriptional activity and acted dominantly negative on SMAD4 and receptor-regulated SMADs, affecting the transcription of target genes and crucial developmental transcription regulator NKX2-5. The findings revealed a dominant-negative model of disease for SMAD4-I500V, where the continued heterodimerization of the variant perturbed the function of SMAD4 and co-factors, leading to dysregulation of TGF and BMP signaling.
Article
Information Science & Library Science
Jan Higgins, Robert D. Steiner
Summary: The investigation into author use of preprints revealed that around 24% of authors were non-compliant with journal preprint policies, and most preprints and articles were submitted very closely together in timing. Additionally, the similarity between preprints and articles was found to be 83% on average, indicating that preprint posting did not notably impact manuscript content.
LEARNED PUBLISHING
(2021)
Meeting Abstract
Endocrinology & Metabolism
Diane Zastrow, Heather Baudet, Amanda Thomas, Wei Shen, Cindy Si, Meredith Weaver, Jixia Liu, Jenny Goldstein, Courtney Thaxton, Justyne Ross, Stephanie Crowley, C. Lisa Kurtz, Jennifer McGlaughon, Bryce Seifert, Rupa Udani, Kathleen Wallace, Gregory Enns, Annette Feigenbaum, Uta Lichter-Konecki, Elaine Lyon, Marzia Pasquali, Nenad Blau, Deeksha Bali, Michele Caganna, Madhuri Hegde, Sean Mooney, Ozlem Senol, Michael Watson, Catherine Rehder, Robert Steiner, William Craigen, Rong Mao
MOLECULAR GENETICS AND METABOLISM
(2019)
Meeting Abstract
Endocrinology & Metabolism
McKenna Kyriss, Robert Steiner, Brooke Sample, James Weber
MOLECULAR GENETICS AND METABOLISM
(2019)