The Experts below are selected from a list of 63 Experts worldwide ranked by ideXlab platform
Fubing Li - One of the best experts on this subject based on the ideXlab platform.
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A Pro253Arg mutation in fibroblast growth factor receptor 2 (Fgfr2) causes skeleton Malformation mimicking human Apert syndrome by affecting both chondrogenesis and osteogenesis
Bone, 2008Co-Authors: Xiaolan Du, Huabing Qi, Nan Su, Xiaoling Xu, Cuiling Li, Ling Zhao, Zhi Chen, Fubing LiAbstract:Apert syndrome is one of the most severe craniosynostosis that is mainly caused by either a Ser252Trp(S252W) or Pro253Arg(P253R) mutation in fibroblast growth factor receptor 2 (FGFR2). As an autosomal dominant disorder, Apert syndrome is mainly characterized by Skull Malformation resulting from premature fusion of craniofacial sutures, as well as syndactyly, etc. A P253R mutation of FGFR2 results in nearly one-thirds of the cases of Apert syndrome. The pathogenesis of Apert syndrome resulting from P253R mutation of FGFR2 is still not fully understood. Here we reported a knock-in mouse model carrying P253R mutation in Fgfr2. The mutant mice exhibit smaller body size and brachycephaly. Analysis of the mutant Skulls and long bones revealed premature fusion of coronal suture, shortened cranial base and growth plates of long bones. In vitro organ culture studies further revealed that, compared with wild-type littermates, the mutant mice have prematurely fused coronal sutures and retarded long bone growth. Treatment of the cultured calvaria and femur with PD98059, an Erk1/2 inhibitor, resulted in partially alleviated coronal suture fusion and growth retardation offemur respectively. Our data indicated that the P253R mutation in Fgfr2 directly affect intramembranous and endochondral ossification, which resulted in the premature closure of coronal sutures and growth retardation of long bones and cranial base. And the Erk1/2 signaling pathway partially mediated the effects of P253R mutation of Fgfr2 on cranial sutures and long bones.
William Reardon - One of the best experts on this subject based on the ideXlab platform.
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caput membranaceum a novel clinical presentation of zic1 related Skull Malformation and craniosynostosis
American Journal of Medical Genetics Part A, 2020Co-Authors: Erina Sasaki, Angela T Byrne, Dylan J Murray, William ReardonAbstract:We report clinical and radiological features of a patient born with an isolated Skull Malformation of caput membranaceum and partial bicoronal craniosynostosis with a novel, de novo heterozygous missense variant in ZIC1 [NM_003412.3:c.1183C>G, p.(Pro395Ala)]. Caput membranaceum, or boneless Skull, is a rare manifestation of Skull ossification defect. It can result from an isolated, enlarged parietal foramina or it can present as part of skeletal dysplasia syndromes associated with poor mineralization such as hypophosphatasia, osteogenesis imperfecta type II, and Saethre-Chotzen syndrome. Their causative genes are well described. ZIC1, Zinc Finger protein of the cerebellum 1 (OMIM #600470) belongs to ZIC family genes, each encoding a Cys2 His2-type zinc finger domain-containing transcription factors. Recent studies have shown that pathogenic variants in ZIC1 have deleterious effect in developing human central nerves system and Skull bone. ZIC1 related clinical conditions are reported and include cerebellum Malformation, Dandy-Walker Malformation, spinal dysraphism, microcephaly, and craniosynostosis with associated intellectual disability. To-date, there is no report of pathogenic variant in ZIC1 causing isolated caput membranaceum. Our observation adds to the clinical spectrum of ZIC1 related Skull Malformation.
Lianyang Zhang - One of the best experts on this subject based on the ideXlab platform.
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A Ser252Trp Mutation in Fibroblast Growth Factor Receptor 2 (FGFR2) Mimicking Human Apert Syndrome Reveals an Essential Role for FGF Signaling in the Regulation of Endochondral Bone Formation
2013Co-Authors: Peng Chen, Li Zhang, Tujun Weng, Shichang Zhang, Shijin Sun, Mingtao Chang, Bo Zhang, Lianyang ZhangAbstract:A S252W mutation of fibroblast growth factor receptor 2 (FGFR2), which is responsible for nearly two-thirds of Apert syndrome (AS) cases, causes retarded development of the skeleton and Skull Malformation resulting from premature fusion of the craniofacial sutures. We utilized a Fgfr2+/S252W mouse (a knock-in mouse model mimicking human AS) to demonstrate decreased bone mass due to reduced trabecular bone volume, reduced bone mineral density, and shortened growth plates in the long bones. In vitro bone mesenchymal stem cells (BMSCs) culture studies revealed that the mutant mice showed reduced BMSC proliferation, a reduction in chondrogenic differentiation, and reduced mineralization. Our results suggest that these phenomena are caused by up-regulation of p38 and Erk1/2 phosphorylation. Treatment of cultured mutant bone rudiments with SB203580 or PD98059 resulted in partial rescue of the bone growth retardation. The p38 signaling pathway especially was found to be responsible for the retarded long bone development. Our data indicate that the S252W mutation in FGFR2 directly affects endochondral ossification, resulting in growth retardation of the long bone. We also show that the p38 and Erk1/2 signaling pathways partially mediate the effects of the S252W mutation of FGFR2 on long bone development
Xiaolan Du - One of the best experts on this subject based on the ideXlab platform.
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A Pro253Arg mutation in fibroblast growth factor receptor 2 (Fgfr2) causes skeleton Malformation mimicking human Apert syndrome by affecting both chondrogenesis and osteogenesis
Bone, 2008Co-Authors: Xiaolan Du, Huabing Qi, Nan Su, Xiaoling Xu, Cuiling Li, Ling Zhao, Zhi Chen, Fubing LiAbstract:Apert syndrome is one of the most severe craniosynostosis that is mainly caused by either a Ser252Trp(S252W) or Pro253Arg(P253R) mutation in fibroblast growth factor receptor 2 (FGFR2). As an autosomal dominant disorder, Apert syndrome is mainly characterized by Skull Malformation resulting from premature fusion of craniofacial sutures, as well as syndactyly, etc. A P253R mutation of FGFR2 results in nearly one-thirds of the cases of Apert syndrome. The pathogenesis of Apert syndrome resulting from P253R mutation of FGFR2 is still not fully understood. Here we reported a knock-in mouse model carrying P253R mutation in Fgfr2. The mutant mice exhibit smaller body size and brachycephaly. Analysis of the mutant Skulls and long bones revealed premature fusion of coronal suture, shortened cranial base and growth plates of long bones. In vitro organ culture studies further revealed that, compared with wild-type littermates, the mutant mice have prematurely fused coronal sutures and retarded long bone growth. Treatment of the cultured calvaria and femur with PD98059, an Erk1/2 inhibitor, resulted in partially alleviated coronal suture fusion and growth retardation offemur respectively. Our data indicated that the P253R mutation in Fgfr2 directly affect intramembranous and endochondral ossification, which resulted in the premature closure of coronal sutures and growth retardation of long bones and cranial base. And the Erk1/2 signaling pathway partially mediated the effects of P253R mutation of Fgfr2 on cranial sutures and long bones.
Teresa A. Simon - One of the best experts on this subject based on the ideXlab platform.
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Pregnancy outcomes following exposure to abatacept during pregnancy.
Seminars in Arthritis and Rheumatism, 2015Co-Authors: Monica Kumar, Laura Ray, Sudha Vemuri, Teresa A. SimonAbstract:Abstract Objective To characterize pregnancy outcomes following maternal and paternal exposure to abatacept, using clinical trial and post-marketing data available to the manufacturer. Methods All confirmed cases of pregnancy with outcome data reported to the manufacturer up to September 1, 2014 were included. Sources included clinical trials, spontaneously reported (unsolicited) post-marketing cases, and the Organization of Teratology Information Specialists registry. Details recorded included number of live births, spontaneous abortions and terminations, pregnancy complications, and congenital anomalies. Results A total of 161 pregnancies with known outcomes were identified between 1995 and September 2014: 151 were following maternal exposure to abatacept and 10 were following paternal exposure. Seven of 86 (8.1%) live births following maternal exposure had congenital anomalies (cleft lip/cleft palate, congenital aortic anomaly, meningocele, pyloric stenosis, Skull Malformation, ventricular septal defect/congenital arterial Malformation, and Down׳s syndrome with premature rupture of membranes at 17 weeks that resulted in a live birth via cesarean section and subsequent infant death). In addition, 59 of the 151 (39.0%) cases with maternal exposure resulted in abortions (40 spontaneous and 19 elective). Of the 10 pregnancies with paternal exposure, there were nine live births and one elective abortion, with no congenital abnormalities identified and no fetal deaths. Conclusions Based on these data, there does not appear to be a pattern of congenital anomalies following maternal or paternal exposure to abatacept. No cases of vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, or limb abnormalities (VACTERL) were noted. Spontaneous abortion rates were within expected range. Abatacept should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.