A case of Fibrodysplasia Ossificans Progressiva associated with a novel variant of the ACVR1 gene

Abstract Background Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disease characterized by congenital malformation of the great toes and progressive heterotopic ossification of soft tissues leading to cumulative disability. The genetic cause of FOP are mutations in the ACV...
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Autor*in:	Serena Cappato [verfasserIn] Rasa Traberg [verfasserIn] Jolita Gintautiene [verfasserIn] Federico Zara [verfasserIn] Renata Bocciardi [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	Activin A ACVR1 BMP signaling Fibrodysplasia Ossificans Progressiva p.R258W

Übergeordnetes Werk:	In: Molecular Genetics & Genomic Medicine - Wiley, 2014, 9(2021), 10, Seite n/a-n/a
Übergeordnetes Werk:	volume:9 ; year:2021 ; number:10 ; pages:n/a-n/a

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1002/mgg3.1774

Katalog-ID:	DOAJ076297772

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520			\|a Abstract Background Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disease characterized by congenital malformation of the great toes and progressive heterotopic ossification of soft tissues leading to cumulative disability. The genetic cause of FOP are mutations in the ACVR1 gene that encodes a type I receptor of Bone Morphogenetic Proteins. The most recurrent mutation in FOP patients is R206H affecting the Glycine‐Serine rich domain and causing the hyper‐activation of the receptor and the responsivity to the non‐canonical ligand, Activin A. In the present study, we described a 3‐years old child with early and highly suggestive clinical features of FOP who was found negative for the recurrent p.R206H substitution. Methods Molecular screening of the whole ACVR1 coding sequence and functional characterization in transfection‐based assays. Results and Conclusions We identified a novel, de novo variant in the fifth ACVR1 coding exon (NM_001111067.4:c.772A<T; NP_001104537.1:p.(R258W)). This substitution, never reported in association with FOP, affects a conserved arginine residue in the kinase domain of the protein. In silico analysis predicted the pathogenicity of this substitution, demonstrated by in vitro assays showing that the p.R258W ACVR1 mutated receptor acquires the ability to transduce the aberrant Activin A‐mediated signaling, as observed for the gene variants associated with FOP.
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allfields	10.1002/mgg3.1774 doi (DE-627)DOAJ076297772 (DE-599)DOAJ58b92b79a3a946e98f486780a9b02f10 DE-627 ger DE-627 rakwb eng QH426-470 Serena Cappato verfasserin aut A case of Fibrodysplasia Ossificans Progressiva associated with a novel variant of the ACVR1 gene 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disease characterized by congenital malformation of the great toes and progressive heterotopic ossification of soft tissues leading to cumulative disability. The genetic cause of FOP are mutations in the ACVR1 gene that encodes a type I receptor of Bone Morphogenetic Proteins. The most recurrent mutation in FOP patients is R206H affecting the Glycine‐Serine rich domain and causing the hyper‐activation of the receptor and the responsivity to the non‐canonical ligand, Activin A. In the present study, we described a 3‐years old child with early and highly suggestive clinical features of FOP who was found negative for the recurrent p.R206H substitution. Methods Molecular screening of the whole ACVR1 coding sequence and functional characterization in transfection‐based assays. Results and Conclusions We identified a novel, de novo variant in the fifth ACVR1 coding exon (NM_001111067.4:c.772A<T; NP_001104537.1:p.(R258W)). This substitution, never reported in association with FOP, affects a conserved arginine residue in the kinase domain of the protein. In silico analysis predicted the pathogenicity of this substitution, demonstrated by in vitro assays showing that the p.R258W ACVR1 mutated receptor acquires the ability to transduce the aberrant Activin A‐mediated signaling, as observed for the gene variants associated with FOP. Activin A ACVR1 BMP signaling Fibrodysplasia Ossificans Progressiva p.R258W Genetics Rasa Traberg verfasserin aut Jolita Gintautiene verfasserin aut Federico Zara verfasserin aut Renata Bocciardi verfasserin aut In Molecular Genetics & Genomic Medicine Wiley, 2014 9(2021), 10, Seite n/a-n/a (DE-627)769222234 (DE-600)2734884-2 23249269 nnns volume:9 year:2021 number:10 pages:n/a-n/a https://doi.org/10.1002/mgg3.1774 kostenfrei https://doaj.org/article/58b92b79a3a946e98f486780a9b02f10 kostenfrei https://doi.org/10.1002/mgg3.1774 kostenfrei https://doaj.org/toc/2324-9269 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021 10 n/a-n/a
spelling	10.1002/mgg3.1774 doi (DE-627)DOAJ076297772 (DE-599)DOAJ58b92b79a3a946e98f486780a9b02f10 DE-627 ger DE-627 rakwb eng QH426-470 Serena Cappato verfasserin aut A case of Fibrodysplasia Ossificans Progressiva associated with a novel variant of the ACVR1 gene 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disease characterized by congenital malformation of the great toes and progressive heterotopic ossification of soft tissues leading to cumulative disability. The genetic cause of FOP are mutations in the ACVR1 gene that encodes a type I receptor of Bone Morphogenetic Proteins. The most recurrent mutation in FOP patients is R206H affecting the Glycine‐Serine rich domain and causing the hyper‐activation of the receptor and the responsivity to the non‐canonical ligand, Activin A. In the present study, we described a 3‐years old child with early and highly suggestive clinical features of FOP who was found negative for the recurrent p.R206H substitution. Methods Molecular screening of the whole ACVR1 coding sequence and functional characterization in transfection‐based assays. Results and Conclusions We identified a novel, de novo variant in the fifth ACVR1 coding exon (NM_001111067.4:c.772A<T; NP_001104537.1:p.(R258W)). This substitution, never reported in association with FOP, affects a conserved arginine residue in the kinase domain of the protein. In silico analysis predicted the pathogenicity of this substitution, demonstrated by in vitro assays showing that the p.R258W ACVR1 mutated receptor acquires the ability to transduce the aberrant Activin A‐mediated signaling, as observed for the gene variants associated with FOP. Activin A ACVR1 BMP signaling Fibrodysplasia Ossificans Progressiva p.R258W Genetics Rasa Traberg verfasserin aut Jolita Gintautiene verfasserin aut Federico Zara verfasserin aut Renata Bocciardi verfasserin aut In Molecular Genetics & Genomic Medicine Wiley, 2014 9(2021), 10, Seite n/a-n/a (DE-627)769222234 (DE-600)2734884-2 23249269 nnns volume:9 year:2021 number:10 pages:n/a-n/a https://doi.org/10.1002/mgg3.1774 kostenfrei https://doaj.org/article/58b92b79a3a946e98f486780a9b02f10 kostenfrei https://doi.org/10.1002/mgg3.1774 kostenfrei https://doaj.org/toc/2324-9269 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021 10 n/a-n/a
allfields_unstemmed	10.1002/mgg3.1774 doi (DE-627)DOAJ076297772 (DE-599)DOAJ58b92b79a3a946e98f486780a9b02f10 DE-627 ger DE-627 rakwb eng QH426-470 Serena Cappato verfasserin aut A case of Fibrodysplasia Ossificans Progressiva associated with a novel variant of the ACVR1 gene 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disease characterized by congenital malformation of the great toes and progressive heterotopic ossification of soft tissues leading to cumulative disability. The genetic cause of FOP are mutations in the ACVR1 gene that encodes a type I receptor of Bone Morphogenetic Proteins. The most recurrent mutation in FOP patients is R206H affecting the Glycine‐Serine rich domain and causing the hyper‐activation of the receptor and the responsivity to the non‐canonical ligand, Activin A. In the present study, we described a 3‐years old child with early and highly suggestive clinical features of FOP who was found negative for the recurrent p.R206H substitution. Methods Molecular screening of the whole ACVR1 coding sequence and functional characterization in transfection‐based assays. Results and Conclusions We identified a novel, de novo variant in the fifth ACVR1 coding exon (NM_001111067.4:c.772A<T; NP_001104537.1:p.(R258W)). This substitution, never reported in association with FOP, affects a conserved arginine residue in the kinase domain of the protein. In silico analysis predicted the pathogenicity of this substitution, demonstrated by in vitro assays showing that the p.R258W ACVR1 mutated receptor acquires the ability to transduce the aberrant Activin A‐mediated signaling, as observed for the gene variants associated with FOP. Activin A ACVR1 BMP signaling Fibrodysplasia Ossificans Progressiva p.R258W Genetics Rasa Traberg verfasserin aut Jolita Gintautiene verfasserin aut Federico Zara verfasserin aut Renata Bocciardi verfasserin aut In Molecular Genetics & Genomic Medicine Wiley, 2014 9(2021), 10, Seite n/a-n/a (DE-627)769222234 (DE-600)2734884-2 23249269 nnns volume:9 year:2021 number:10 pages:n/a-n/a https://doi.org/10.1002/mgg3.1774 kostenfrei https://doaj.org/article/58b92b79a3a946e98f486780a9b02f10 kostenfrei https://doi.org/10.1002/mgg3.1774 kostenfrei https://doaj.org/toc/2324-9269 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021 10 n/a-n/a
allfieldsGer	10.1002/mgg3.1774 doi (DE-627)DOAJ076297772 (DE-599)DOAJ58b92b79a3a946e98f486780a9b02f10 DE-627 ger DE-627 rakwb eng QH426-470 Serena Cappato verfasserin aut A case of Fibrodysplasia Ossificans Progressiva associated with a novel variant of the ACVR1 gene 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disease characterized by congenital malformation of the great toes and progressive heterotopic ossification of soft tissues leading to cumulative disability. The genetic cause of FOP are mutations in the ACVR1 gene that encodes a type I receptor of Bone Morphogenetic Proteins. The most recurrent mutation in FOP patients is R206H affecting the Glycine‐Serine rich domain and causing the hyper‐activation of the receptor and the responsivity to the non‐canonical ligand, Activin A. In the present study, we described a 3‐years old child with early and highly suggestive clinical features of FOP who was found negative for the recurrent p.R206H substitution. Methods Molecular screening of the whole ACVR1 coding sequence and functional characterization in transfection‐based assays. Results and Conclusions We identified a novel, de novo variant in the fifth ACVR1 coding exon (NM_001111067.4:c.772A<T; NP_001104537.1:p.(R258W)). This substitution, never reported in association with FOP, affects a conserved arginine residue in the kinase domain of the protein. In silico analysis predicted the pathogenicity of this substitution, demonstrated by in vitro assays showing that the p.R258W ACVR1 mutated receptor acquires the ability to transduce the aberrant Activin A‐mediated signaling, as observed for the gene variants associated with FOP. Activin A ACVR1 BMP signaling Fibrodysplasia Ossificans Progressiva p.R258W Genetics Rasa Traberg verfasserin aut Jolita Gintautiene verfasserin aut Federico Zara verfasserin aut Renata Bocciardi verfasserin aut In Molecular Genetics & Genomic Medicine Wiley, 2014 9(2021), 10, Seite n/a-n/a (DE-627)769222234 (DE-600)2734884-2 23249269 nnns volume:9 year:2021 number:10 pages:n/a-n/a https://doi.org/10.1002/mgg3.1774 kostenfrei https://doaj.org/article/58b92b79a3a946e98f486780a9b02f10 kostenfrei https://doi.org/10.1002/mgg3.1774 kostenfrei https://doaj.org/toc/2324-9269 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021 10 n/a-n/a
allfieldsSound	10.1002/mgg3.1774 doi (DE-627)DOAJ076297772 (DE-599)DOAJ58b92b79a3a946e98f486780a9b02f10 DE-627 ger DE-627 rakwb eng QH426-470 Serena Cappato verfasserin aut A case of Fibrodysplasia Ossificans Progressiva associated with a novel variant of the ACVR1 gene 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disease characterized by congenital malformation of the great toes and progressive heterotopic ossification of soft tissues leading to cumulative disability. The genetic cause of FOP are mutations in the ACVR1 gene that encodes a type I receptor of Bone Morphogenetic Proteins. The most recurrent mutation in FOP patients is R206H affecting the Glycine‐Serine rich domain and causing the hyper‐activation of the receptor and the responsivity to the non‐canonical ligand, Activin A. In the present study, we described a 3‐years old child with early and highly suggestive clinical features of FOP who was found negative for the recurrent p.R206H substitution. Methods Molecular screening of the whole ACVR1 coding sequence and functional characterization in transfection‐based assays. Results and Conclusions We identified a novel, de novo variant in the fifth ACVR1 coding exon (NM_001111067.4:c.772A<T; NP_001104537.1:p.(R258W)). This substitution, never reported in association with FOP, affects a conserved arginine residue in the kinase domain of the protein. In silico analysis predicted the pathogenicity of this substitution, demonstrated by in vitro assays showing that the p.R258W ACVR1 mutated receptor acquires the ability to transduce the aberrant Activin A‐mediated signaling, as observed for the gene variants associated with FOP. Activin A ACVR1 BMP signaling Fibrodysplasia Ossificans Progressiva p.R258W Genetics Rasa Traberg verfasserin aut Jolita Gintautiene verfasserin aut Federico Zara verfasserin aut Renata Bocciardi verfasserin aut In Molecular Genetics & Genomic Medicine Wiley, 2014 9(2021), 10, Seite n/a-n/a (DE-627)769222234 (DE-600)2734884-2 23249269 nnns volume:9 year:2021 number:10 pages:n/a-n/a https://doi.org/10.1002/mgg3.1774 kostenfrei https://doaj.org/article/58b92b79a3a946e98f486780a9b02f10 kostenfrei https://doi.org/10.1002/mgg3.1774 kostenfrei https://doaj.org/toc/2324-9269 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021 10 n/a-n/a
language	English
source	In Molecular Genetics & Genomic Medicine 9(2021), 10, Seite n/a-n/a volume:9 year:2021 number:10 pages:n/a-n/a
sourceStr	In Molecular Genetics & Genomic Medicine 9(2021), 10, Seite n/a-n/a volume:9 year:2021 number:10 pages:n/a-n/a
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Activin A ACVR1 BMP signaling Fibrodysplasia Ossificans Progressiva p.R258W Genetics
isfreeaccess_bool	true
container_title	Molecular Genetics & Genomic Medicine
authorswithroles_txt_mv	Serena Cappato @@aut@@ Rasa Traberg @@aut@@ Jolita Gintautiene @@aut@@ Federico Zara @@aut@@ Renata Bocciardi @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	769222234
id	DOAJ076297772
language_de	englisch
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The genetic cause of FOP are mutations in the ACVR1 gene that encodes a type I receptor of Bone Morphogenetic Proteins. The most recurrent mutation in FOP patients is R206H affecting the Glycine‐Serine rich domain and causing the hyper‐activation of the receptor and the responsivity to the non‐canonical ligand, Activin A. In the present study, we described a 3‐years old child with early and highly suggestive clinical features of FOP who was found negative for the recurrent p.R206H substitution. Methods Molecular screening of the whole ACVR1 coding sequence and functional characterization in transfection‐based assays. Results and Conclusions We identified a novel, de novo variant in the fifth ACVR1 coding exon (NM_001111067.4:c.772A<T; NP_001104537.1:p.(R258W)). This substitution, never reported in association with FOP, affects a conserved arginine residue in the kinase domain of the protein. 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callnumber-first	Q - Science
author	Serena Cappato
spellingShingle	Serena Cappato misc QH426-470 misc Activin A misc ACVR1 misc BMP signaling misc Fibrodysplasia Ossificans Progressiva misc p.R258W misc Genetics A case of Fibrodysplasia Ossificans Progressiva associated with a novel variant of the ACVR1 gene
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topic_title	QH426-470 A case of Fibrodysplasia Ossificans Progressiva associated with a novel variant of the ACVR1 gene Activin A ACVR1 BMP signaling Fibrodysplasia Ossificans Progressiva p.R258W
topic	misc QH426-470 misc Activin A misc ACVR1 misc BMP signaling misc Fibrodysplasia Ossificans Progressiva misc p.R258W misc Genetics
topic_unstemmed	misc QH426-470 misc Activin A misc ACVR1 misc BMP signaling misc Fibrodysplasia Ossificans Progressiva misc p.R258W misc Genetics
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title	A case of Fibrodysplasia Ossificans Progressiva associated with a novel variant of the ACVR1 gene
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title_full	A case of Fibrodysplasia Ossificans Progressiva associated with a novel variant of the ACVR1 gene
author_sort	Serena Cappato
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title_sort	case of fibrodysplasia ossificans progressiva associated with a novel variant of the acvr1 gene
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title_auth	A case of Fibrodysplasia Ossificans Progressiva associated with a novel variant of the ACVR1 gene
abstract	Abstract Background Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disease characterized by congenital malformation of the great toes and progressive heterotopic ossification of soft tissues leading to cumulative disability. The genetic cause of FOP are mutations in the ACVR1 gene that encodes a type I receptor of Bone Morphogenetic Proteins. The most recurrent mutation in FOP patients is R206H affecting the Glycine‐Serine rich domain and causing the hyper‐activation of the receptor and the responsivity to the non‐canonical ligand, Activin A. In the present study, we described a 3‐years old child with early and highly suggestive clinical features of FOP who was found negative for the recurrent p.R206H substitution. Methods Molecular screening of the whole ACVR1 coding sequence and functional characterization in transfection‐based assays. Results and Conclusions We identified a novel, de novo variant in the fifth ACVR1 coding exon (NM_001111067.4:c.772A<T; NP_001104537.1:p.(R258W)). This substitution, never reported in association with FOP, affects a conserved arginine residue in the kinase domain of the protein. In silico analysis predicted the pathogenicity of this substitution, demonstrated by in vitro assays showing that the p.R258W ACVR1 mutated receptor acquires the ability to transduce the aberrant Activin A‐mediated signaling, as observed for the gene variants associated with FOP.
abstractGer	Abstract Background Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disease characterized by congenital malformation of the great toes and progressive heterotopic ossification of soft tissues leading to cumulative disability. The genetic cause of FOP are mutations in the ACVR1 gene that encodes a type I receptor of Bone Morphogenetic Proteins. The most recurrent mutation in FOP patients is R206H affecting the Glycine‐Serine rich domain and causing the hyper‐activation of the receptor and the responsivity to the non‐canonical ligand, Activin A. In the present study, we described a 3‐years old child with early and highly suggestive clinical features of FOP who was found negative for the recurrent p.R206H substitution. Methods Molecular screening of the whole ACVR1 coding sequence and functional characterization in transfection‐based assays. Results and Conclusions We identified a novel, de novo variant in the fifth ACVR1 coding exon (NM_001111067.4:c.772A<T; NP_001104537.1:p.(R258W)). This substitution, never reported in association with FOP, affects a conserved arginine residue in the kinase domain of the protein. In silico analysis predicted the pathogenicity of this substitution, demonstrated by in vitro assays showing that the p.R258W ACVR1 mutated receptor acquires the ability to transduce the aberrant Activin A‐mediated signaling, as observed for the gene variants associated with FOP.
abstract_unstemmed	Abstract Background Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disease characterized by congenital malformation of the great toes and progressive heterotopic ossification of soft tissues leading to cumulative disability. The genetic cause of FOP are mutations in the ACVR1 gene that encodes a type I receptor of Bone Morphogenetic Proteins. The most recurrent mutation in FOP patients is R206H affecting the Glycine‐Serine rich domain and causing the hyper‐activation of the receptor and the responsivity to the non‐canonical ligand, Activin A. In the present study, we described a 3‐years old child with early and highly suggestive clinical features of FOP who was found negative for the recurrent p.R206H substitution. Methods Molecular screening of the whole ACVR1 coding sequence and functional characterization in transfection‐based assays. Results and Conclusions We identified a novel, de novo variant in the fifth ACVR1 coding exon (NM_001111067.4:c.772A<T; NP_001104537.1:p.(R258W)). This substitution, never reported in association with FOP, affects a conserved arginine residue in the kinase domain of the protein. In silico analysis predicted the pathogenicity of this substitution, demonstrated by in vitro assays showing that the p.R258W ACVR1 mutated receptor acquires the ability to transduce the aberrant Activin A‐mediated signaling, as observed for the gene variants associated with FOP.
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title_short	A case of Fibrodysplasia Ossificans Progressiva associated with a novel variant of the ACVR1 gene
url	https://doi.org/10.1002/mgg3.1774 https://doaj.org/article/58b92b79a3a946e98f486780a9b02f10 https://doaj.org/toc/2324-9269
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The genetic cause of FOP are mutations in the ACVR1 gene that encodes a type I receptor of Bone Morphogenetic Proteins. The most recurrent mutation in FOP patients is R206H affecting the Glycine‐Serine rich domain and causing the hyper‐activation of the receptor and the responsivity to the non‐canonical ligand, Activin A. In the present study, we described a 3‐years old child with early and highly suggestive clinical features of FOP who was found negative for the recurrent p.R206H substitution. Methods Molecular screening of the whole ACVR1 coding sequence and functional characterization in transfection‐based assays. Results and Conclusions We identified a novel, de novo variant in the fifth ACVR1 coding exon (NM_001111067.4:c.772A<T; NP_001104537.1:p.(R258W)). This substitution, never reported in association with FOP, affects a conserved arginine residue in the kinase domain of the protein. In silico analysis predicted the pathogenicity of this substitution, demonstrated by in vitro assays showing that the p.R258W ACVR1 mutated receptor acquires the ability to transduce the aberrant Activin A‐mediated signaling, as observed for the gene variants associated with FOP.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Activin A</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">ACVR1</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">BMP signaling</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Fibrodysplasia Ossificans Progressiva</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">p.R258W</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Genetics</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rasa Traberg</subfield><subfield code="e">verfasserin</subfield><subfield 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A case of Fibrodysplasia Ossificans Progressiva associated with a novel variant of the ACVR1 gene

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