Read by QxMD icon Read

Smith lemli opitz syndrome

Anika V Prabhu, Winnie Luu, Dianfan Li, Laura J Sharpe, Andrew J Brown
The conversion of 7-dehydrocholesterol to cholesterol, the final step of cholesterol synthesis in the Kandutsch-Russell pathway, is catalyzed by the enzyme 7-dehydrocholesterol reductase (DHCR7). Homozygous or compound heterozygous mutations in DHCR7 lead to the developmental disease Smith-Lemli-Opitz syndrome, which can also result in fetal mortality, highlighting the importance of this enzyme in human development and survival. Besides serving as a substrate for DHCR7, 7-dehydrocholesterol is also a precursor of vitamin D via the action of ultraviolet light on the skin...
September 30, 2016: Progress in Lipid Research
Ayfer Aslan, Alp Ozgun Borcek, Selma Pamukcuoglu, M Kemali Baykaner
BACKGROUND: Smith-Lemli-Opitz Syndrome (SLOS) is a rare hereditary autosomal recessive disorder with broken cholesterol synthesis causing by 7-dehydrocholesterol reductase deficiency. Although the clinical features and pathogenesis is well-defined, it is unknown whether there is a relationship between SLOS and neoplastic processes, especially brain neoplasms. PURPOSE: We aimed to attract the attentions to any possibility of relation between SLOS and intracranial tumor development via a pediatric case with both intracranial high-grade neuroglial tumor and SLOS, and thus to contribute an additional data to the literature on togetherness of these two clinical conditions...
August 15, 2016: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
Anika V Prabhu, Winnie Luu, Laura J Sharpe, Andrew J Brown
Cholesterol is essential for survival, but too much or too little can cause disease. Thus, cholesterol levels must be kept within close margins. 7-dehydrocholesterol reductase (DHCR7) is a terminal enzyme of cholesterol synthesis, and is essential for embryonic development. Largely, DHCR7 research is associated with the developmental disease Smith-Lemli-Opitz syndrome, which is caused by mutations in the DHCR7 gene. However, little is known about what regulates DHCR7 activity. Here we provide evidence that phosphorylation plays a role in controlling DHCR7 activity, which may provide a means to divert flux from cholesterol synthesis to vitamin D production...
August 9, 2016: Journal of Steroid Biochemistry and Molecular Biology
Christopher A Wassif, Lisa Kratz, Susan E Sparks, Courtney Wheeler, Simona Bianconi, Andrea Gropman, Karim A Calis, Richard I Kelley, Elaine Tierney, Forbes D Porter
BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation/cognitive impairment syndrome characterized by the accumulation of 7-dehydrocholesterol, a precursor sterol of cholesterol. Simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor that crosses the blood-brain barrier, has been proposed for the treatment of SLOS based on in vitro and in vivo studies suggesting that simvastatin increases the expression of hypomorphic DHCR7 alleles. METHODS: Safety and efficacy of simvastatin therapy in 23 patients with mild to typical SLOS were evaluated in a randomized, double-blind, placebo-controlled trial...
August 11, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
M R Boland, N P Tatonetti
Mendelian diseases contain important biological information regarding developmental effects of gene mutations that can guide drug discovery and toxicity efforts. In this review, we focus on Smith-Lemli-Opitz syndrome (SLOS), a rare Mendelian disease characterized by compound heterozygous mutations in 7-dehydrocholesterol reductase (DHCR7) resulting in severe fetal deformities. We present a compilation of SLOS-inducing DHCR7 mutations and the geographic distribution of those mutations in healthy and diseased populations...
October 2016: Pharmacogenomics Journal
Christine Vianey-Saban, Cécile Acquaviva, David Cheillan, Sophie Collardeau-Frachon, Laurent Guibaud, Cécile Pagan, Magali Pettazzoni, Monique Piraud, Antonin Lamazière, Roseline Froissart
Inborn errors of metabolism (IEMs) that present with abnormal imaging findings in the second half of pregnancy are mainly lysosomal storage disorders (LSDs), cholesterol synthesis disorders (CSDs), glycogen storage disorder type IV (GSD IV), peroxisomal disorders, mitochondrial fatty acid oxidation defects (FAODs), organic acidurias, aminoacidopathies, congenital disorders of glycosylation (CDGs), and transaldolase deficiency. Their biological investigation requires fetal material. The supernatant of amniotic fluid (AF) is useful for the analysis of mucopolysaccharides, oligosaccharides, sialic acid, lysosphingolipids and some enzyme activities for LSDs, 7- and 8-dehydrocholesterol, desmosterol and lathosterol for CSDs, acylcarnitines for FAODs, organic acids for organic acidurias, and polyols for transaldolase deficiency...
September 2016: Journal of Inherited Metabolic Disease
Myriam Gou-Fàbregas, Anna Macià, Carlos Anerillas, Marta Vaquero, Mariona Jové, Sanjay Jain, Joan Ribera, Mario Encinas
Smith-Lemli-Opitz syndrome (SLOS) is a rare disorder of cholesterol synthesis. Affected individuals exhibit growth failure, intellectual disability and a broad spectrum of developmental malformations. Among them, renal agenesis or hypoplasia, decreased innervation of the gut, and ptosis are consistent with impaired Ret signaling. Ret is a receptor tyrosine kinase that achieves full activity when recruited to lipid rafts. Mice mutant for Ret are born with no kidneys and enteric neurons, and display sympathetic nervous system defects causing ptosis...
2016: Scientific Reports
András Balajthy, Sándor Somodi, Zoltán Pethő, Mária Péter, Zoltán Varga, Gabriella P Szabó, György Paragh, László Vígh, György Panyi, Péter Hajdu
In vitro manipulation of membrane sterol level affects the regulation of ion channels and consequently certain cellular functions; however, a comprehensive study that confirms the pathophysiological significance of these results is missing. The malfunction of 7-dehydrocholesterol (7DHC) reductase in Smith-Lemli-Opitz syndrome (SLOS) leads to the elevation of the 7-dehydrocholesterol level in the plasma membrane. T lymphocytes were isolated from SLOS patients to assess the effect of the in vivo altered membrane sterol composition on the operation of the voltage-gated Kv1...
August 2016: Pflügers Archiv: European Journal of Physiology
Agata Szpera-Goździewicz, Mariola Ropacka-Lesiak, Paweł Rzymski, Grzegorz H Bręborowicz
The aim of the study was to present a case of Smith-Lemli-Opitz syndrome (SLOS) in a fetus of a 33-year-old patient. At 31 weeks of gestation, the following fetal malformations were detected on an ultrasound: atrioventricular septal defect (AVSD), aortic coarctation, shortening of the lower limbs, narrow forehead, hyperthelorism, micrognathia, anteverted nares, ambiguous genitalia, and signs of intrauterine growth restriction. The baby died 11 days after birth. Further genetic screening of the parents revealed the 7-DHCR enzyme mutation in both of them...
2016: Ginekologia Polska
Kurt A Freeman, Erin Olufs, Megan Tudor, Jean-Baptiste Roullet, Robert D Steiner
OBJECTIVE: Smith-Lemli-Opitz syndrome (SLOS) is a rare genetic disorder characterized by cholesterol synthesis impairment. A host of physical, developmental, and behavioral presentations are associated with SLOS, many of which have been related with disorder severity. Sleep disturbance is commonly reported in SLOS. This study is the first to examine the association between sleep disturbance and biomarkers of cholesterol synthesis defect. METHOD: Twenty youth with SLOS participated...
June 2016: Journal of Developmental and Behavioral Pediatrics: JDBP
Navdar Sever, Randall K Mann, Libin Xu, William J Snell, Carmen I Hernandez-Lara, Ned A Porter, Philip A Beachy
Cellular lipids are speculated to act as key intermediates in Hedgehog signal transduction, but their precise identity and function remain enigmatic. In an effort to identify such lipids, we pursued a Hedgehog pathway inhibitory activity that is particularly abundant in flagellar lipids of Chlamydomonas reinhardtii, resulting in the purification and identification of ergosterol endoperoxide, a B-ring oxysterol. A mammalian analog of ergosterol, 7-dehydrocholesterol (7-DHC), accumulates in Smith-Lemli-Opitz syndrome, a human genetic disease that phenocopies deficient Hedgehog signaling and is caused by genetic loss of 7-DHC reductase...
May 24, 2016: Proceedings of the National Academy of Sciences of the United States of America
Stephanie M Cologna, Christine Shieh, Cynthia L Toth, Antony Cougnoux, Kathryn R Burkert, Simona E Bianconi, Christopher A Wassif, Forbes D Porter
Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive, multiple malformation syndrome with neurocognitive impairment. SLOS arises from mutations in the 7-dehydrocholesterol reductase gene which results in impaired enzymatic conversion of 7-dehydrocholesterol to cholesterol. In the current work, we sought to measure proteins that were altered in the cerebrospinal fluid from SLOS patients compared to pediatric controls. Using a multi-analyte antibody-based assay, we found that 12 proteins are altered in SLOS patients...
August 2016: American Journal of Medical Genetics. Part A
A M Petrov, M R Kasimov, A L Zefirov
Cholesterol is an important constituent of cell membranes and plays a crucial role in the compartmentalization of the plasma membrane and signaling. Brain cholesterol accounts for a large proportion of the body's total cholesterol, existing in two pools: the plasma membranes of neurons and glial cells and the myelin membranes . Cholesterol has been recently shown to be important for synaptic transmission, and a link between cholesterol metabolism defects and neurodegenerative disorders is now recognized. Many neurodegenerative diseases are characterized by impaired cholesterol turnover in the brain...
January 2016: Acta Naturae
Hye-Young H Kim, Zeljka Korade, Keri A Tallman, Wei Liu, C David Weaver, Karoly Mirnics, Ned A Porter
A small library of pharmacologically active compounds (the NIH Clinical Collection) was assayed in Neuro2a cells to determine their effect on the last step in the biosynthesis of cholesterol, the transformation of 7-dehydrocholesterol (7-DHC) to cholesterol promoted by 7-dehydrocholesterol reductase, DHCR7. Of some 727 compounds in the NIH Clinical Collection, over 30 compounds significantly increased 7-DHC in Neuro2a cells when assayed at 1 μM. Active compounds that increased 7-DHC with a Z-score of +3 or greater generally gave rise to modest decreases in desmosterol and increases in lanosterol levels...
May 16, 2016: Chemical Research in Toxicology
Audrey Thurm, Elaine Tierney, Cristan Farmer, Phebe Albert, Lisa Joseph, Susan Swedo, Simona Bianconi, Irena Bukelis, Courtney Wheeler, Geeta Sarphare, Diane Lanham, Christopher A Wassif, Forbes D Porter
BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive inborn error of cholesterol metabolism syndrome with neurocognitive manifestations. SLOS is the result of mutations in the gene encoding the 7-dehydrocholesterol reductase, which results in the elevation of the cholesterol precursor 7-dehydrocholesterol (7-DHC). Previous reports indicate that intellectual disability, behavioral disturbances, and autism symptoms are frequently part of the SLOS behavioral phenotype...
2016: Journal of Neurodevelopmental Disorders
Zhexing Wen, Hongjun Song, Guo-li Ming
No abstract text is available yet for this article.
April 2016: Nature Medicine
Kevin R Francis, Amy N Ton, Yao Xin, Peter E O'Halloran, Christopher A Wassif, Nasir Malik, Ian M Williams, Celine V Cluzeau, Niraj S Trivedi, William J Pavan, Wonhwa Cho, Heiner Westphal, Forbes D Porter
Smith-Lemli-Opitz syndrome (SLOS) is a malformation disorder caused by mutations in DHCR7, which impair the reduction of 7-dehydrocholesterol (7DHC) to cholesterol. SLOS results in cognitive impairment, behavioral abnormalities and nervous system defects, though neither affected cell types nor impaired signaling pathways are fully understood. Whether 7DHC accumulation or cholesterol loss is primarily responsible for disease pathogenesis is also unclear. Using induced pluripotent stem cells (iPSCs) from subjects with SLOS, we identified cellular defects that lead to precocious neuronal specification within SLOS derived neural progenitors...
April 2016: Nature Medicine
William J Griffiths, Jonas Abdel-Khalik, Peter J Crick, Michael Ogundare, Cedric H Shackleton, Karin Tuschl, Mei Kwun Kwok, Brian W Bigger, Andrew A Morris, Akira Honda, Libin Xu, Ned A Porter, Ingemar Björkhem, Peter T Clayton, Yuqin Wang
Smith-Lemli-Opitz syndrome (SLOS) is a severe autosomal recessive disorder resulting from defects in the cholesterol synthesising enzyme 7-dehydrocholesterol reductase (Δ(7)-sterol reductase, DHCR7, EC leading to a build-up of the cholesterol precursor 7-dehydrocholesterol (7-DHC) in tissues and blood plasma. Although the underling enzyme deficiency associated with SLOS is clear there are likely to be multiple mechanisms responsible for SLOS pathology. In an effort to learn more of the aetiology of SLOS we have analysed plasma from SLOS patients to search for metabolites derived from 7-DHC which may be responsible for some of the pathology...
March 11, 2016: Journal of Steroid Biochemistry and Molecular Biology
Arianna Tucci, Luisa Ronzoni, Carlo Arduino, Paola Salmin, Susanna Esposito, Donatella Milani
BACKGROUND: Smith Lemli Opitz syndrome (SLOS; OMIM #270400) is an autosomal recessive metabolic disorder caused by mutations in the DHCR7 gene. SLOS is characterized by a plethora of abnormalities involving mainly the brain and the genitalia but also the cardiac, skeletal and gastroenteric system, typical dysmorphic facial features, and variable degrees of developmental delay and intellectual disability (ID). SLOS has a broad phenotypic spectrum, ranging from multiple congenital malformation syndrome, to mild developmental delay and minor malformations...
2016: BMC Medical Genetics
Kritika Jangid, Aurelian Jovita Alexander, Nadathur Doraiswamy Jayakumar, Sheeja Varghese, Pratibha Ramani
Ankyloglossia or tongue-tie is a congenital anomaly affecting the tongue, which is characterized by thick, short lingual frenulum. This condition causes many difficulties such as limited tongue protrusion, breastfeeding difficulties, speech impairment and lack of self-confidence. It is very rarely associated with any other congenital craniofacial disorders such as cleft lip, X-linked cleft palate, Van der Woude syndrome, Smith-Lemli-Opitz syndrome, Orofacial digital syndrome, Beckwith Weidman syndrome or Simpson-Golabi-Behmel syndrome...
November 2015: Journal of Indian Society of Periodontology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"