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1. Whole genome sequencing identifies associations for nonsyndromic sagittal craniosynostosis with the intergenic region of BMP2 and noncoding RNA gene LINC01428

Author

Musolf, Anthony M., Justice, Cristina M., Erdogan-Yildirim, Zeynep, Goovaerts, Seppe, Cuellar, Araceli, Shaffer, John R., Marazita, Mary L., Claes, Peter, Weinberg, Seth M., Li, Jae, Senders, Craig, Zwienenberg, Marike, Simeonov, Emil, Kaneva, Radka, Roscioli, Tony, Di Pietro, Lorena, Barba, Marta, Lattanzi, Wanda, Cunningham, Michael L., Romitti, Paul A., and Boyadjiev, Simeon A.

Published
2024
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2. Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape

Author

Goovaerts, Seppe, Hoskens, Hanne, Eller, Ryan J., Herrick, Noah, Musolf, Anthony M., Justice, Cristina M., Yuan, Meng, Naqvi, Sahin, Lee, Myoung Keun, Vandermeulen, Dirk, Szabo-Rogers, Heather L., Romitti, Paul A., Boyadjiev, Simeon A., Marazita, Mary L., Shaffer, John R., Shriver, Mark D., Wysocka, Joanna, Walsh, Susan, Weinberg, Seth M., and Claes, Peter

Published
2023
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3. Regulatory elements in SEM1-DLX5-DLX6 (7q21.3) locus contribute to genetic control of coronal nonsyndromic craniosynostosis and bone density-related traits

Author

Nicoletti, Paola, Zafer, Samreen, Matok, Lital, Irron, Inbar, Patrick, Meidva, Haklai, Rotem, Evangelista, John Erol, Marino, Giacomo B., Ma’ayan, Avi, Sewda, Anshuman, Holmes, Greg, Britton, Sierra R., Lee, Won Jun, Wu, Meng, Ru, Ying, Arnaud, Eric, Botto, Lorenzo, Brody, Lawrence C., Byren, Jo C., Caggana, Michele, Carmichael, Suzan L., Cilliers, Deirdre, Conway, Kristin, Crawford, Karen, Cuellar, Araceli, Di Rocco, Federico, Engel, Michael, Fearon, Jeffrey, Feldkamp, Marcia L., Finnell, Richard, Fisher, Sarah, Freudlsperger, Christian, Garcia-Fructuoso, Gemma, Hagge, Rhinda, Heuzé, Yann, Harshbarger, Raymond J., Hobbs, Charlotte, Howley, Meredith, Jenkins, Mary M., Johnson, David, Justice, Cristina M., Kane, Alex, Kay, Denise, Gosain, Arun Kumar, Langlois, Peter, Legal-Mallet, Laurence, Lin, Angela E., Mills, James L., Morton, Jenny E.V., Noons, Peter, Olshan, Andrew, Persing, John, Phipps, Julie M., Redett, Richard, Reefhuis, Jennita, Rizk, Elias, Samson, Thomas D., Shaw, Gary M., Sicko, Robert, Smith, Nataliya, Staffenberg, David, Stoler, Joan, Sweeney, Elizabeth, Taub, Peter J., Timberlake, Andrew T., Topczewska, Jolanta, Wall, Steven A., Wilson, Alexander F., Wilson, Louise C., Boyadjiev, Simeon A., Wilkie, Andrew O.M., Richtsmeier, Joan T., Jabs, Ethylin Wang, Romitti, Paul A., Karasik, David, Birnbaum, Ramon Y., and Peter, Inga

Published
2024
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4. A genome-wide association study implicates the BMP7 locus as a risk factor for nonsyndromic metopic craniosynostosis

Author

Justice, Cristina M, Cuellar, Araceli, Bala, Krithi, Sabourin, Jeremy A, Cunningham, Michael L, Crawford, Karen, Phipps, Julie M, Zhou, Yan, Cilliers, Deirdre, Byren, Jo C, Johnson, David, Wall, Steven A, Morton, Jenny EV, Noons, Peter, Sweeney, Elizabeth, Weber, Astrid, Rees, Katie EM, Wilson, Louise C, Simeonov, Emil, Kaneva, Radka, Yaneva, Nadezhda, Georgiev, Kiril, Bussarsky, Assen, Senders, Craig, Zwienenberg, Marike, Boggan, James, Roscioli, Tony, Tamburrini, Gianpiero, Barba, Marta, Conway, Kristin, Sheffield, Val C, Brody, Lawrence, Mills, James L, Kay, Denise, Sicko, Robert J, Langlois, Peter H, Tittle, Rachel K, Botto, Lorenzo D, Jenkins, Mary M, LaSalle, Janine M, Lattanzi, Wanda, Wilkie, Andrew OM, Wilson, Alexander F, Romitti, Paul A, and Boyadjiev, Simeon A

Subjects
Genetics, Complementary and Alternative Medicine, Paediatrics and Reproductive Medicine, Genetics & Heredity, Reproductive medicine
Abstract

Our previous genome-wide association study (GWAS) for sagittal nonsyndromic craniosynostosis (sNCS) provided important insights into the genetics of midline CS. In this study, we performed a GWAS for a second midline NCS, metopic NCS (mNCS), using 215 non-Hispanic white case-parent triads. We identified six variants with genome-wide significance (P ≤ 5 × 10–8): rs781716 (P = 4.71 × 10–9; odds ratio [OR] = 2.44) intronic to SPRY3; rs6127972 (P = 4.41 × 10–8; OR = 2.17) intronic to BMP7; rs62590971 (P = 6.22 × 10–9; OR = 0.34), located ~ 155 kb upstream from TGIF2LX; and rs2522623, rs2573826, and rs2754857, all intronic to PCDH11X (P = 1.76 × 10–8, OR = 0.45; P = 3.31 × 10–8, OR = 0.45; P = 1.09 × 10–8, OR = 0.44, respectively). We performed a replication study of these variants using an independent non-Hispanic white sample of 194 unrelated mNCS cases and 333 unaffected controls; only the association for rs6127972 (P = 0.004, OR = 1.45; meta-analysis P = 1.27 × 10–8, OR = 1.74) was replicated. Our meta-analysis examining single nucleotide polymorphisms common to both our mNCS and sNCS studies showed the strongest association for rs6127972 (P = 1.16 × 10–6). Our imputation analysis identified a linkage disequilibrium block encompassing rs6127972, which contained an enhancer overlapping a CTCF transcription factor binding site (chr20:55,798,821–55,798,917) that was significantly hypomethylated in mesenchymal stem cells derived from fused metopic compared to open sutures from the same probands. This study provides additional insights into genetic factors in midline CS.

Published
2020

6. SMAD6 variants in craniosynostosis: genotype and phenotype evaluation

Author

Calpena, Eduardo, Cuellar, Araceli, Bala, Krithi, Swagemakers, Sigrid M.A., Koelling, Nils, McGowan, Simon J., Phipps, Julie M., Balasubramanian, Meena, Cunningham, Michael L., Douzgou, Sofia, Lattanzi, Wanda, Morton, Jenny E.V., Shears, Deborah, Weber, Astrid, Wilson, Louise C., Lord, Helen, Lester, Tracy, Johnson, David, Wall, Steven A., Twigg, Stephen R.F., Mathijssen, Irene M.J., Boardman-Pretty, Freya, Boyadjiev, Simeon A., and Wilkie, Andrew O.M.

Published
2020
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8. Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency.

Author

Valayannopoulos, Vassili, Malinova, Vera, Honzík, Tomas, Balwani, Manisha, Breen, Catherine, Deegan, Patrick B, Enns, Gregory M, Jones, Simon A, Kane, John P, Stock, Eveline O, Tripuraneni, Radhika, Eckert, Stephen, Schneider, Eugene, Hamilton, Gavin, Middleton, Michael S, Sirlin, Claude, Kessler, Bruce, Bourdon, Christopher, Boyadjiev, Simeon A, Sharma, Reena, Twelves, Chris, Whitley, Chester B, and Quinn, Anthony G

Subjects
Liver, Humans, Wolman Disease, Alanine Transaminase, Aspartate Aminotransferases, Lipids, Recombinant Proteins, Drug Administration Schedule, Adult, Middle Aged, Female, Male, Sterol Esterase, Young Adult, Dyslipidemia, Enzyme replacement, Fatty liver, Hepatomegaly, Lysosomal storage, Gastroenterology & Hepatology, Clinical Sciences, Public Health and Health Services
Abstract

Background & aimsLysosomal acid lipase deficiency is an autosomal recessive enzyme deficiency resulting in lysosomal accumulation of cholesteryl esters and triglycerides. LAL-CL04, an ongoing extension study, investigates the long-term effects of sebelipase alfa, a recombinant human lysosomal acid lipase.MethodsSebelipase alfa (1mg/kg or 3mg/kg) was infused every-other-week to eligible subjects. Safety and tolerability assessments, including liver function, lipid profiles and liver volume assessment, were carried out at regular intervals.Results216 infusions were administered to eight adult subjects through week 52 during LAL-CL04. At week 52, mean alanine aminotransferase and aspartate aminotransferase levels were normal with mean change from baseline of -58% and -40%. Mean changes for low-density lipoprotein, total cholesterol, triglyceride and high-density lipoprotein were -60%, -39%, -36%, and +29%, respectively. Mean liver volume by magnetic resonance imaging and hepatic proton density fat fraction decreased (12% and 55%, respectively). Adverse events were mainly mild and unrelated to sebelipase alfa. Infusion-related reactions were uncommon: three events of moderate severity were reported in two subjects; one patient's event was suggestive of a hypersensitivity-like reaction, but additional testing did not confirm this, and the subject has successfully re-started sebelipase alfa. Of samples tested to date, no anti-drug antibodies have been detected.ConclusionsLong-term dosing with sebelipase alfa in lysosomal acid lipase-deficient patients is well tolerated and produces sustained reductions in transaminases, improvements in serum lipid profile and reduction in the hepatic fat fraction. A randomized, placebo-controlled phase 3 trial in children and adults is underway (ARISE: NCT01757184).

Published
2014

9. Familial incidence and associated symptoms in a population of individuals with nonsyndromic craniosynostosis

Author

Greenwood, Jaclyn, Flodman, Pamela, Osann, Kathryn, Boyadjiev, Simeon A, and Kimonis, Virginia

Subjects
Biological Sciences, Genetics, Dental/Oral and Craniofacial Disease, Rare Diseases, Pediatric, Congenital Structural Anomalies, Clinical Research, 2.1 Biological and endogenous factors, Adolescent, Child, Child, Preschool, Cranial Sutures, Craniosynostoses, Female, Health Surveys, Humans, Incidence, Infant, Male, Pedigree, Phenotype, Risk Factors, Young Adult, familial incidence, nonsyndromic craniosynostosis, symptoms, Clinical Sciences, Genetics & Heredity
Abstract

PurposeCraniosynostosis is a common cranial malformation occurring in 1 per 2,000-2,500 births. Isolated defects (nonsyndromic) occur in ~75% of cases and are thought to have multifactorial etiology. It is believed that each suture synostosis is a distinct disease, with varying phenotypes and recurrence rates.MethodsWe analyzed family histories of 660 mutation-negative nonsyndromic craniosynostosis patients and symptoms in 189 of these patients.ResultsThe incidence rate of craniosynostosis was highest for first-degree relatives of probands with metopic craniosynostosis (6.4%), followed by those with complex craniosynostosis (4.9%), sagittal craniosynostosis (3.8%), lambdoid craniosynostosis (3.9%), and coronal craniosynostosis (0.7%). Across all suture types, siblings had a greater craniosynostosis incidence rate than parents (7.5 vs. 2.3%). In phenotype comparisons, patients with complex craniosynostosis had the highest frequency of reported symptoms and those with sagittal craniosynostosis had the lowest. Ear infections, palate abnormalities, and hearing problems were more common in complex craniosynostosis patients. Visual problems were more common in coronal craniosynostosis, and metopic craniosynostosis patients noted increased frequency of chronic cough.ConclusionOur data suggest that the genetic component of nonsyndromic craniosynostosis appears to be suture specific. The incidence rate of craniosynostosis among first-degree relatives varies by suture and family member. Additionally, the phenotype of each suture synostosis shows both unique and shared features.

Published
2014

10. A genome-wide association study identifies susceptibility loci for nonsyndromic sagittal craniosynostosis near BMP2 and within BBS9

Author

Justice, Cristina M, Yagnik, Garima, Kim, Yoonhee, Peter, Inga, Jabs, Ethylin Wang, Erazo, Monica, Ye, Xiaoqian, Ainehsazan, Edmond, Shi, Lisong, Cunningham, Michael L, Kimonis, Virginia, Roscioli, Tony, Wall, Steven A, Wilkie, Andrew OM, Stoler, Joan, Richtsmeier, Joan T, Heuzé, Yann, Sanchez-Lara, Pedro A, Buckley, Michael F, Druschel, Charlotte M, Mills, James L, Caggana, Michele, Romitti, Paul A, Kay, Denise M, Senders, Craig, Taub, Peter J, Klein, Ophir D, Boggan, James, Zwienenberg-Lee, Marike, Naydenov, Cyrill, Kim, Jinoh, Wilson, Alexander F, and Boyadjiev, Simeon A

Subjects
Biological Sciences, Genetics, Prevention, Rare Diseases, Human Genome, Dental/Oral and Craniofacial Disease, Bone Morphogenetic Protein 2, Cohort Studies, Craniosynostoses, Cytoskeletal Proteins, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Infant, Newborn, Male, Neoplasm Proteins, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Sex Factors, White People, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Sagittal craniosynostosis is the most common form of craniosynostosis, affecting approximately one in 5,000 newborns. We conducted, to our knowledge, the first genome-wide association study for nonsyndromic sagittal craniosynostosis (sNSC) using 130 non-Hispanic case-parent trios of European ancestry (NHW). We found robust associations in a 120-kb region downstream of BMP2 flanked by rs1884302 (P = 1.13 × 10(-14), odds ratio (OR) = 4.58) and rs6140226 (P = 3.40 × 10(-11), OR = 0.24) and within a 167-kb region of BBS9 between rs10262453 (P = 1.61 × 10(-10), OR = 0.19) and rs17724206 (P = 1.50 × 10(-8), OR = 0.22). We replicated the associations to both loci (rs1884302, P = 4.39 × 10(-31) and rs10262453, P = 3.50 × 10(-14)) in an independent NHW population of 172 unrelated probands with sNSC and 548 controls. Both BMP2 and BBS9 are genes with roles in skeletal development that warrant functional studies to further understand the etiology of sNSC.

Published
2012

11. ALX4 gain-of-function mutations in non-syndromic craniosynostosis

Author

Yagnik, Garima, Ghuman, Apar, Kim, Sundon, Stevens, Cristina G., Kimonis, Virginia, Stoler, Joan, Sanchez-Lara, Pedro, Bernstein, Jonathan, Naydenov, Cyril, Drissi, Hicham, Cunningham, Michael L., Kim, Jinoh, and Boyadjiev, Simeon A.

Abstract

Craniosynostosis is the early fusion of one or more sutures of the infant skull and is a common defect occurring in approximately 1 of every 2,500 live births. Non-syndromic craniosynostosis accounts for approximately 80% of all cases and is thought to have strong genetic determinants that are yet to be identified. ALX4 is a homeodomain transcription factor with known involvement in osteoblast regulation. By direct sequencing of the ALX4 coding region in sagittal or sagittal-suture-involved non-syndromic craniosynostosis probands, we identified novel, nonsynonymous, familial variants in three of 203 individuals with NSC. Using dual-luciferase assay we show that two of these variants (V7F and K211E) confer a significant gain-of-function effect on ALX4. Our results suggest that ALX4 variants may have an impact on the genetic etiology of NSC.

Published
2012

12. Differential growth factor adsorption to calvarial osteoblast-secreted extracellular matrices instructs osteoblastic behavior.

Author

Bhat, Archana, Boyadjiev, Simeon A, Senders, Craig W, and Leach, J Kent

Subjects
Skull, Extracellular Matrix, Osteoblasts, Humans, Craniosynostoses, Glucuronidase, Chondroitin ABC Lyase, Case-Control Studies, Substrate Specificity, Osteogenesis, Adsorption, Transforming Growth Factor beta1, Heparan Sulfate Proteoglycans, Bone Morphogenetic Protein 2, Chondroitin Sulfate Proteoglycans, General Science & Technology
Abstract

Craniosynostosis (CS), the premature ossification of cranial sutures, is attributed to increased osteogenic potential of resident osteoblasts, yet the contribution of the surrounding extracellular matrix (ECM) on osteogenic differentiation is unclear. The osteoblast-secreted ECM provides binding sites for cellular adhesion and regulates the transport and signaling of osteoinductive factors secreted by the underlying dura mater. The binding affinity of each osteoinductive factor for the ECM may amplify or mute its relative effect, thus contributing to the rate of suture fusion. The purpose of this paper was to examine the role of ECM composition derived from calvarial osteoblasts on protein binding and its resultant effect on cell phenotype. We hypothesized that potent osteoinductive proteins present during sutural fusion (e.g., bone morphogenetic protein-2 (BMP-2) and transforming growth factor beta-1 (TGF-β1)) would exhibit distinct differences in binding when exposed to ECMs generated by human calvarial osteoblasts from unaffected control individuals (CI) or CS patients. Decellularized ECMs produced by osteoblasts from CI or CS patients were incubated in the presence of BMP-2 or TGF-β1, and the affinity of each protein was analyzed. The contribution of ECM composition to protein binding was interrogated by enzymatically modulating proteoglycan content within the ECM. BMP-2 had a similar binding affinity for each ECM, while TGF-β1 had a greater affinity for ECMs produced by osteoblasts from CI compared to CS patients. Enzymatic treatment of ECMs reduced protein binding. CS osteoblasts cultured on enzymatically-treated ECMs secreted by osteoblasts from CI patients in the presence of BMP-2 exhibited impaired osteogenic differentiation compared to cells on untreated ECMs. These data demonstrate the importance of protein binding to cell-secreted ECMs and confirm that protein-ECM interactions have an important role in directing osteoblastic differentiation of calvarial osteoblasts.

Published
2011

13. A Unique Point Mutation in the PMP22 Gene Is Associated with Charcot-Marie-Tooth Disease and Deafness

Author

Kovach, Margaret J, Lin, Jing-Ping, Boyadjiev, Simeon, Campbell, Kathleen, Mazzeo, Larry, Herman, Kristin, Rimer, Lisa A, Frank, William, Llewellyn, Barbara, Jabs, Ethylin Wang, Gelber, David, and Kimonis, Virginia E

Subjects
Biological Sciences, Genetics, Neurosciences, Neurodegenerative, Charcot-Marie-Tooth Disease, Peripheral Neuropathy, Biotechnology, Brain Disorders, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Amino Acid Sequence, Base Sequence, DNA Primers, Deafness, Female, Genetic Linkage, Haplotypes, Humans, Male, Molecular Sequence Data, Mutation, Myelin Proteins, Pedigree, Point Mutation, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Charcot-Marie-Tooth disease (CMT) with deafness is clinically distinct among the genetically heterogeneous group of CMT disorders. Molecular studies in a large family with autosomal dominant CMT and deafness have not been reported. The present molecular study involves a family with progressive features of CMT and deafness, originally reported by Kousseff et al. Genetic analysis of 70 individuals (31 affected, 28 unaffected, and 11 spouses) revealed linkage to markers on chromosome 17p11.2-p12, with a maximum LOD score of 9.01 for marker D17S1357 at a recombination fraction of .03. Haplotype analysis placed the CMT-deafness locus between markers D17S839 and D17S122, a approximately 0.6-Mb interval. This critical region lies within the CMT type 1A duplication region and excludes MYO15, a gene coding an unconventional myosin that causes a form of autosomal recessive deafness called DFNB3. Affected individuals from this family do not have the common 1.5-Mb duplication of CMT type 1A. Direct sequencing of the candidate peripheral myelin protein 22 (PMP22) gene detected a unique G-->C transversion in the heterozygous state in all affected individuals, at position 248 in coding exon 3, predicted to result in an Ala67Pro substitution in the second transmembrane domain of PMP22.

Published
1999

14. Joint Multi-Ancestry and Admixed GWAS Reveals the Complex Genetics behind Human Cranial Vault Shape

Author

Goovaerts, Seppe, primary, Hoskens, Hanne, additional, Eller, Ryan J, additional, Herrick, Noah, additional, Musolf, Anthony M, additional, Justice, Cristina M, additional, Yuan, Meng, additional, Naqvi, Sahin, additional, Lee, Myoung Keun, additional, Vandermeulen, Dirk, additional, Szabo-Rogers, Heather L, additional, Romitti, Paul A, additional, Boyadjiev, Simeon A, additional, Marazita, Mary L, additional, Shaffer, John R, additional, Shriver, Mark D, additional, Wysocka, Joanna, additional, Walsh, Susan, additional, Weinberg, Seth M, additional, and Claes, Peter, additional

Published
2022
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16. TM4SF20 Ancestral Deletion and Susceptibility to a Pediatric Disorder of Early Language Delay and Cerebral White Matter Hyperintensities

Author

Wiszniewski, Wojciech, Hunter, Jill V., Hanchard, Neil A., Willer, Jason R., Shaw, Chad, Tian, Qi, Illner, Anna, Wang, Xueqing, Cheung, Sau W., Patel, Ankita, Campbell, Ian M., Gelowani, Violet, Hixson, Patricia, Ester, Audrey R., Azamian, Mahshid S., Potocki, Lorraine, Zapata, Gladys, Hernandez, Patricia P., Ramocki, Melissa B., Santos-Cortez, Regie L.P., Wang, Gao, York, Michele K., Justice, Monica J., Chu, Zili D., Bader, Patricia I., Omo-Griffith, Lisa, Madduri, Nirupama S., Scharer, Gunter, Crawford, Heather P., Yanatatsaneejit, Pattamawadee, Eifert, Anna, Kerr, Jeffery, Bacino, Carlos A., Franklin, Adiaha I.A., Goin-Kochel, Robin P., Simpson, Gayle, Immken, Ladonna, Haque, Muhammad E., Stosic, Marija, Williams, Misti D., Morgan, Thomas M., Pruthi, Sumit, Omary, Reed, Boyadjiev, Simeon A., Win, Kay K., Thida, Aye, Hurles, Matthew, Hibberd, Martin Lloyd, Khor, Chiea Chuen, Van Vinh Chau, Nguyen, Gallagher, Thomas E., Mutirangura, Apiwat, Stankiewicz, Pawel, Beaudet, Arthur L., Maletic-Savatic, Mirjana, Rosenfeld, Jill A., Shaffer, Lisa G., Davis, Erica E., Belmont, John W., Dunstan, Sarah, Simmons, Cameron P., Bonnen, Penelope E., Leal, Suzanne M., Katsanis, Nicholas, Lupski, James R., and Lalani, Seema R.

Published
2013
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20. Targeted Sequencing of Candidate Regions Associated with Sagittal and Metopic Nonsyndromic Craniosynostosis

Author

Justice, Cristina M., primary, Musolf, Anthony M., additional, Cuellar, Araceli, additional, Lattanzi, Wanda, additional, Simeonov, Emil, additional, Kaneva, Radka, additional, Paschall, Justin, additional, Cunningham, Michael, additional, Wilkie, Andrew O. M., additional, Wilson, Alexander F., additional, Romitti, Paul A., additional, and Boyadjiev, Simeon A., additional

Published
2022
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21. The genetic overlap between osteoporosis and craniosynostosis

Author

Kague, Erika, Medina-Gomez, Carolina, Boyadjiev, Simeon A., Rivadeneira, Fernando, Kague, Erika, Medina-Gomez, Carolina, Boyadjiev, Simeon A., and Rivadeneira, Fernando

Abstract

Osteoporosis is the most prevalent bone condition in the ageing population. This systemic disease is characterized by microarchitectural deterioration of bone, leading to increased fracture risk. In the past 15 years, genome-wide association studies (GWAS), have pinpointed hundreds of loci associated with bone mineral density (BMD), helping elucidate the underlying molecular mechanisms and genetic architecture of fracture risk. However, the challenge remains in pinpointing causative genes driving GWAS signals as a pivotal step to drawing the translational therapeutic roadmap. Recently, a skull BMD-GWAS uncovered an intriguing intersection with craniosynostosis, a congenital anomaly due to premature suture fusion in the skull. Here, we recapitulate the genetic contribution to both osteoporosis and craniosynostosis, describing the biological underpinnings of this overlap and using zebrafish models to leverage the functional investigation of genes associated with skull development and systemic skeletal homeostasis.

Published
2022

22. Phenotype Severity in the Bladder Exstrophy-Epispadias Complex: Analysis of Genetic and Nongenetic Contributing Factors in 441 Families from North America and Europe

Author

Reutter, Heiko, Boyadjiev, Simeon A., Gambhir, Lisa, Ebert, Anne-Karoline, Rösch, Wolfgang H., Stein, Raimund, Schröder, Annette, Boemers, Thomas M., Bartels, Enrika, Vogt, Hannes, Utsch, Boris, Müller, Martin, Detlefsen, Birte, Zwink, Nadine, Rogenhofer, Sebastian, Gobet, Rita, Beckers, Goedele M.A., Bökenkamp, Arend, Kajbafzadeh, Abdol-Mohammad, Jaureguizar, Enrique, Draaken, Markus, Lakshmanan, Yegappan, Gearhart, John P., Ludwig, Michael, Nöthen, Markus M., and Jenetzky, Ekkehart

Published
2011
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24. Muenke syndrome: An international multicenter natural history study

Author

Kruszka, Paul, Addissie, Yonit A., Yarnell, Colin M. P., Hadley, Donald W., Guillen Sacoto, Maria J., Platte, Petra, Paelecke, Yvonne, Collmann, Hartmut, Snow, Nicole, Schweitzer, Tilmann, Boyadjiev, Simeon A., Aravidis, Christos, Hall, Samantha E., Mulliken, John B., Roscioli, Tony, and Muenke, Maximilian

Published
2016
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27. Genome-wide association study and mouse expression data identify a highly conserved 32 kb intergenic region between WNT3 and WNT9b as possible susceptibility locus for isolated classic exstrophy of the bladder

Author

Reutter, Heiko, Draaken, Markus, Pennimpede, Tracie, Wittler, Lars, Brockschmidt, Felix F., Ebert, Anne-Karolin, Bartels, Enrika, Rösch, Wolfgang, Boemers, Thomas M., Hirsch, Karin, Schmiedeke, Eberhard, Meesters, Christian, Becker, Tim, Stein, Raimund, Utsch, Boris, Mangold, Elisabeth, Nordenskjöld, Agneta, Barker, Gillian, Kockum, Christina Clementsson, Zwink, Nadine, Holmdahl, Gundula, Läckgren, Göran, Jenetzky, Ekkehart, Feitz, Wouter F.J., Marcelis, Carlo, Wijers, Charlotte H.W., Van Rooij, Iris A.L.M., Gearhart, John P., Herrmann, Bernhard G., Ludwig, Michael, Boyadjiev, Simeon A., Nöthen, Markus M., and Mattheisen, Manuel

Published
2014
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34. Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia

Author

Paznekas, William A., Boyadjiev, Simeon A., Shapiro, Robert E., Daniels, Otto, Wollnik, Bernd, Keegan, Catherine E., Innis, Jeffrey W., Dinulos, Mary Beth, Christian, Cathy, Hannibal, Mark C., and Jabs, Ethylin Wang

Subjects
Dysplasia -- Genetic aspects, Gene mutations -- Physiological aspects, Genetic disorders -- Research, Human genetics -- Research, Biological sciences
Published
2003

36. OTX2 mutations contribute to the otocephaly-dysgnathia complex

Author

Chassaing, Nicolas, Sorrentino, Susanna, Davis, Erica E, Martin-Coignard, Dominique, Iacovelli, Anthony, Paznekas, William, Webb, Bryn D, Faye-Petersen, Ona, Encha-Razavi, Férechté, Lequeux, Leopoldine, Vigouroux, Adeline, Yesilyurt, Ahmet, Boyadjiev, Simeon A, Kayserili, Hülya, Loget, Philippe, Carles, Dominique, Sergi, Consolato, Puvabanditsin, Surasak, Chen, Chih-Ping, Etchevers, Heather C, Katsanis, Nicholas, Mercer, Catherine L, Calvas, Patrick, and Jabs, Ethylin Wang

Published
2012
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41. Correction: SMAD6 variants in craniosynostosis: genotype and phenotype evaluation

Author

Calpena, Eduardo, primary, Cuellar, Araceli, additional, Bala, Krithi, additional, Swagemakers, Sigrid M.A., additional, Koelling, Nils, additional, McGowan, Simon J., additional, Phipps, Julie M., additional, Balasubramanian, Meena, additional, Cunningham, Michael L., additional, Douzgou, Sofia, additional, Lattanzi, Wanda, additional, Morton, Jenny E.V., additional, Shears, Deborah, additional, Weber, Astrid, additional, Wilson, Louise C., additional, Lord, Helen, additional, Lester, Tracy, additional, Johnson, David, additional, Wall, Steven A., additional, Twigg, Stephen R.F., additional, Mathijssen, Irene M.J., additional, Boardman-Pretty, Freya, additional, Boyadjiev, Simeon A., additional, and Wilkie, Andrew O.M., additional

Published
2020
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48. Collagen has a unique SEC24 preference for efficient export from the endoplasmic reticulum.

Author

Lu, Chung‐Ling, Ortmeier, Steven, Brudvig, Jon, Moretti, Tamara, Cain, Jacob, Boyadjiev, Simeon A., Weimer, Jill M., and Kim, Jinoh

Subjects
COLLAGEN, OSTEOGENESIS imperfecta, ENDOPLASMIC reticulum, SECRETION, DYSPLASIA, FIBRONECTINS
Abstract

SEC24 is mainly involved in cargo sorting during COPII vesicle assembly. There are four SEC24 paralogs (A–D) in vertebrates, which are classified into two subgroups (SEC24A/B and SEC24C/D). Pathological mutations in SEC24D cause osteogenesis imperfecta with craniofacial dysplasia in humans. sec24d mutant fish also recapitulate the phenotypes. Consistent with the skeletal phenotypes, the secretion of collagen was severely defective in mutant fish, emphasizing the importance of SEC24D in collagen secretion. However, SEC24D patient‐derived fibroblasts show only a mild secretion phenotype, suggesting tissue‐specificity in the secretion process. Using Sec24d KO mice and cultured cells, we show that SEC24A and SEC24B also contribute to endoplasmic reticulum (ER) export of procollagen. In contrast, fibronectin 1 requires either SEC24C or SEC24D for ER export. On the basis of our results, we propose that procollagen interacts with multiple SEC24 paralogs for efficient export from the ER, and that this is the basis for tissue‐specific phenotypes resulting from SEC24 paralog deficiency. [ABSTRACT FROM AUTHOR]

Published
2022
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