A Novel Mutation in Fibroblast Growth Factor 23 Gene as a Cause of Tumoral Calcinosis
Context: Tumoral calcinosis is a disease characterized by ectopic calcification and hyperphosphatemia due to enhanced renal tubular phosphate reabsorption. Fibroblast growth factor (FGF)23 was identified as a responsible factor in hypophosphatemic diseases caused by renal phosphate leak. Objective:...
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| creator | Araya, Kaori Fukumoto, Seiji Backenroth, Rebecca Takeuchi, Yasuhiro Nakayama, Kounosuke Ito, Nobuaki Yoshii, Nozomi Yamazaki, Yuji Yamashita, Takeyoshi Silver, Justin Igarashi, Takashi Fujita, Toshiro |
| description | Context: Tumoral calcinosis is a disease characterized by ectopic calcification and hyperphosphatemia due to enhanced renal tubular phosphate reabsorption. Fibroblast growth factor (FGF)23 was identified as a responsible factor in hypophosphatemic diseases caused by renal phosphate leak.
Objective: The objective of the study was to analyze the involvement of FGF23 in the development of tumoral calcinosis.
Design: Serum FGF23 level was evaluated in a patient with tumoral calcinosis by two kinds of ELISA: full-length assay that detects only full-length FGF23 with phosphate-lowering activity and C-terminal assay that measures full-length as well as C-terminal fragment of FGF23. FGF23 gene was analyzed by direct sequencing of PCR products, and mutant FGF23 was analyzed by Western blotting after expression in mammalian cells.
Patients: A family of tumoral calcinosis patients were studied.
Results: Serum FGF23 was extremely high when measured by C-terminal assay. In contrast, it was low normal by full-length assay. Analysis of FGF23 gene detected a serine to phenylalanine mutation in codon 129. No wild-type allele of this codon was found in the patient. The brother of the proband showed the same base change. When this mutant FGF23 was expressed in vitro, full-length and N-terminal fragments were barely detectable by Western blotting, whereas C-terminal fragment with the same molecular weight as that from wild-type FGF23 could be detected.
Conclusion: The production and serum level of C-terminal fragment of FGF23 are increased in this patient with tumoral calcinosis. Together with the recent similar report of FGF23 mutation, impaired action of full-length FGF23 seems to result in tumoral calcinosis. |
| doi_str_mv | 10.1210/jc.2005-0301 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_68663082</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>17386440</sourcerecordid><originalsourceid>FETCH-LOGICAL-c498t-269a8b4d7a7abfe41a945819e0dbd8703942d53b5b60dd61e55aa35da5cb6e5e3</originalsourceid><addsrcrecordid>eNqF0M9rFDEUwPEgFrtWb54lF3tyajL5NTmWxV2FWi8teBtekjeYZTZZkxnF_76z7EIvgqfA48N74UvIO85ueMvZp52_aRlTDROMvyArbqVqDLfmJVkx1vLGmvbHJXld644xLqUSr8gl10et7Io83tL7_BtH-m2eYIo50ZjoJrqS3Qh1otuS_0w_6Qb8lAttBd1iQgqVAl3DXJHmgT7M-1xgXAajjynXWN-QiwHGim_P7xV53Hx-WH9p7r5vv65v7xovbTc1rbbQORkMGHADSg7L5ztukQUXOsOElW1QwimnWQiao1IAQgVQ3mlUKK7I9WnvoeRfM9ap38fqcRwhYZ5rrzutBeva_0JuRKelZAv8eIK-5FoLDv2hxD2Uvz1n_bF3v_P9sXd_LLjw9-e9s9tjeMbnwAv4cAZQPYxDgeRjfXaGGyu4Wpw4OUwh-xITHgrW2u_yXNKS8N_nnwDbPJds</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17386440</pqid></control><display><type>article</type><title>A Novel Mutation in Fibroblast Growth Factor 23 Gene as a Cause of Tumoral Calcinosis</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Araya, Kaori ; Fukumoto, Seiji ; Backenroth, Rebecca ; Takeuchi, Yasuhiro ; Nakayama, Kounosuke ; Ito, Nobuaki ; Yoshii, Nozomi ; Yamazaki, Yuji ; Yamashita, Takeyoshi ; Silver, Justin ; Igarashi, Takashi ; Fujita, Toshiro</creator><creatorcontrib>Araya, Kaori ; Fukumoto, Seiji ; Backenroth, Rebecca ; Takeuchi, Yasuhiro ; Nakayama, Kounosuke ; Ito, Nobuaki ; Yoshii, Nozomi ; Yamazaki, Yuji ; Yamashita, Takeyoshi ; Silver, Justin ; Igarashi, Takashi ; Fujita, Toshiro</creatorcontrib><description>Context: Tumoral calcinosis is a disease characterized by ectopic calcification and hyperphosphatemia due to enhanced renal tubular phosphate reabsorption. Fibroblast growth factor (FGF)23 was identified as a responsible factor in hypophosphatemic diseases caused by renal phosphate leak.
Objective: The objective of the study was to analyze the involvement of FGF23 in the development of tumoral calcinosis.
Design: Serum FGF23 level was evaluated in a patient with tumoral calcinosis by two kinds of ELISA: full-length assay that detects only full-length FGF23 with phosphate-lowering activity and C-terminal assay that measures full-length as well as C-terminal fragment of FGF23. FGF23 gene was analyzed by direct sequencing of PCR products, and mutant FGF23 was analyzed by Western blotting after expression in mammalian cells.
Patients: A family of tumoral calcinosis patients were studied.
Results: Serum FGF23 was extremely high when measured by C-terminal assay. In contrast, it was low normal by full-length assay. Analysis of FGF23 gene detected a serine to phenylalanine mutation in codon 129. No wild-type allele of this codon was found in the patient. The brother of the proband showed the same base change. When this mutant FGF23 was expressed in vitro, full-length and N-terminal fragments were barely detectable by Western blotting, whereas C-terminal fragment with the same molecular weight as that from wild-type FGF23 could be detected.
Conclusion: The production and serum level of C-terminal fragment of FGF23 are increased in this patient with tumoral calcinosis. Together with the recent similar report of FGF23 mutation, impaired action of full-length FGF23 seems to result in tumoral calcinosis.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jc.2005-0301</identifier><identifier>PMID: 16030159</identifier><identifier>CODEN: JCEMAZ</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>Adult ; Biological and medical sciences ; Blotting, Western ; Calcinosis - etiology ; Calcinosis - genetics ; Cells, Cultured ; Culture Media, Conditioned ; DNA, Antisense - genetics ; DNA, Complementary - biosynthesis ; DNA, Complementary - genetics ; Endocrinopathies ; Enzyme-Linked Immunosorbent Assay ; Female ; Fibroblast Growth Factors - genetics ; Fundamental and applied biological sciences. Psychology ; Humans ; Medical sciences ; Molecular Weight ; Mutation - physiology ; Neoplasms - complications ; Neoplasms - genetics ; Pedigree ; Phosphates - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Vertebrates: endocrinology ; Vitamin D - metabolism</subject><ispartof>The journal of clinical endocrinology and metabolism, 2005-10, Vol.90 (10), p.5523-5527</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c498t-269a8b4d7a7abfe41a945819e0dbd8703942d53b5b60dd61e55aa35da5cb6e5e3</citedby><cites>FETCH-LOGICAL-c498t-269a8b4d7a7abfe41a945819e0dbd8703942d53b5b60dd61e55aa35da5cb6e5e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17179315$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16030159$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Araya, Kaori</creatorcontrib><creatorcontrib>Fukumoto, Seiji</creatorcontrib><creatorcontrib>Backenroth, Rebecca</creatorcontrib><creatorcontrib>Takeuchi, Yasuhiro</creatorcontrib><creatorcontrib>Nakayama, Kounosuke</creatorcontrib><creatorcontrib>Ito, Nobuaki</creatorcontrib><creatorcontrib>Yoshii, Nozomi</creatorcontrib><creatorcontrib>Yamazaki, Yuji</creatorcontrib><creatorcontrib>Yamashita, Takeyoshi</creatorcontrib><creatorcontrib>Silver, Justin</creatorcontrib><creatorcontrib>Igarashi, Takashi</creatorcontrib><creatorcontrib>Fujita, Toshiro</creatorcontrib><title>A Novel Mutation in Fibroblast Growth Factor 23 Gene as a Cause of Tumoral Calcinosis</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Context: Tumoral calcinosis is a disease characterized by ectopic calcification and hyperphosphatemia due to enhanced renal tubular phosphate reabsorption. Fibroblast growth factor (FGF)23 was identified as a responsible factor in hypophosphatemic diseases caused by renal phosphate leak.
Objective: The objective of the study was to analyze the involvement of FGF23 in the development of tumoral calcinosis.
Design: Serum FGF23 level was evaluated in a patient with tumoral calcinosis by two kinds of ELISA: full-length assay that detects only full-length FGF23 with phosphate-lowering activity and C-terminal assay that measures full-length as well as C-terminal fragment of FGF23. FGF23 gene was analyzed by direct sequencing of PCR products, and mutant FGF23 was analyzed by Western blotting after expression in mammalian cells.
Patients: A family of tumoral calcinosis patients were studied.
Results: Serum FGF23 was extremely high when measured by C-terminal assay. In contrast, it was low normal by full-length assay. Analysis of FGF23 gene detected a serine to phenylalanine mutation in codon 129. No wild-type allele of this codon was found in the patient. The brother of the proband showed the same base change. When this mutant FGF23 was expressed in vitro, full-length and N-terminal fragments were barely detectable by Western blotting, whereas C-terminal fragment with the same molecular weight as that from wild-type FGF23 could be detected.
Conclusion: The production and serum level of C-terminal fragment of FGF23 are increased in this patient with tumoral calcinosis. Together with the recent similar report of FGF23 mutation, impaired action of full-length FGF23 seems to result in tumoral calcinosis.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Calcinosis - etiology</subject><subject>Calcinosis - genetics</subject><subject>Cells, Cultured</subject><subject>Culture Media, Conditioned</subject><subject>DNA, Antisense - genetics</subject><subject>DNA, Complementary - biosynthesis</subject><subject>DNA, Complementary - genetics</subject><subject>Endocrinopathies</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Fibroblast Growth Factors - genetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Molecular Weight</subject><subject>Mutation - physiology</subject><subject>Neoplasms - complications</subject><subject>Neoplasms - genetics</subject><subject>Pedigree</subject><subject>Phosphates - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Vertebrates: endocrinology</subject><subject>Vitamin D - metabolism</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0M9rFDEUwPEgFrtWb54lF3tyajL5NTmWxV2FWi8teBtekjeYZTZZkxnF_76z7EIvgqfA48N74UvIO85ueMvZp52_aRlTDROMvyArbqVqDLfmJVkx1vLGmvbHJXld644xLqUSr8gl10et7Io83tL7_BtH-m2eYIo50ZjoJrqS3Qh1otuS_0w_6Qb8lAttBd1iQgqVAl3DXJHmgT7M-1xgXAajjynXWN-QiwHGim_P7xV53Hx-WH9p7r5vv65v7xovbTc1rbbQORkMGHADSg7L5ztukQUXOsOElW1QwimnWQiao1IAQgVQ3mlUKK7I9WnvoeRfM9ap38fqcRwhYZ5rrzutBeva_0JuRKelZAv8eIK-5FoLDv2hxD2Uvz1n_bF3v_P9sXd_LLjw9-e9s9tjeMbnwAv4cAZQPYxDgeRjfXaGGyu4Wpw4OUwh-xITHgrW2u_yXNKS8N_nnwDbPJds</recordid><startdate>20051001</startdate><enddate>20051001</enddate><creator>Araya, Kaori</creator><creator>Fukumoto, Seiji</creator><creator>Backenroth, Rebecca</creator><creator>Takeuchi, Yasuhiro</creator><creator>Nakayama, Kounosuke</creator><creator>Ito, Nobuaki</creator><creator>Yoshii, Nozomi</creator><creator>Yamazaki, Yuji</creator><creator>Yamashita, Takeyoshi</creator><creator>Silver, Justin</creator><creator>Igarashi, Takashi</creator><creator>Fujita, Toshiro</creator><general>Endocrine Society</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20051001</creationdate><title>A Novel Mutation in Fibroblast Growth Factor 23 Gene as a Cause of Tumoral Calcinosis</title><author>Araya, Kaori ; Fukumoto, Seiji ; Backenroth, Rebecca ; Takeuchi, Yasuhiro ; Nakayama, Kounosuke ; Ito, Nobuaki ; Yoshii, Nozomi ; Yamazaki, Yuji ; Yamashita, Takeyoshi ; Silver, Justin ; Igarashi, Takashi ; Fujita, Toshiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c498t-269a8b4d7a7abfe41a945819e0dbd8703942d53b5b60dd61e55aa35da5cb6e5e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Calcinosis - etiology</topic><topic>Calcinosis - genetics</topic><topic>Cells, Cultured</topic><topic>Culture Media, Conditioned</topic><topic>DNA, Antisense - genetics</topic><topic>DNA, Complementary - biosynthesis</topic><topic>DNA, Complementary - genetics</topic><topic>Endocrinopathies</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Fibroblast Growth Factors - genetics</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Molecular Weight</topic><topic>Mutation - physiology</topic><topic>Neoplasms - complications</topic><topic>Neoplasms - genetics</topic><topic>Pedigree</topic><topic>Phosphates - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Vertebrates: endocrinology</topic><topic>Vitamin D - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Araya, Kaori</creatorcontrib><creatorcontrib>Fukumoto, Seiji</creatorcontrib><creatorcontrib>Backenroth, Rebecca</creatorcontrib><creatorcontrib>Takeuchi, Yasuhiro</creatorcontrib><creatorcontrib>Nakayama, Kounosuke</creatorcontrib><creatorcontrib>Ito, Nobuaki</creatorcontrib><creatorcontrib>Yoshii, Nozomi</creatorcontrib><creatorcontrib>Yamazaki, Yuji</creatorcontrib><creatorcontrib>Yamashita, Takeyoshi</creatorcontrib><creatorcontrib>Silver, Justin</creatorcontrib><creatorcontrib>Igarashi, Takashi</creatorcontrib><creatorcontrib>Fujita, Toshiro</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Araya, Kaori</au><au>Fukumoto, Seiji</au><au>Backenroth, Rebecca</au><au>Takeuchi, Yasuhiro</au><au>Nakayama, Kounosuke</au><au>Ito, Nobuaki</au><au>Yoshii, Nozomi</au><au>Yamazaki, Yuji</au><au>Yamashita, Takeyoshi</au><au>Silver, Justin</au><au>Igarashi, Takashi</au><au>Fujita, Toshiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Novel Mutation in Fibroblast Growth Factor 23 Gene as a Cause of Tumoral Calcinosis</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2005-10-01</date><risdate>2005</risdate><volume>90</volume><issue>10</issue><spage>5523</spage><epage>5527</epage><pages>5523-5527</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><coden>JCEMAZ</coden><abstract>Context: Tumoral calcinosis is a disease characterized by ectopic calcification and hyperphosphatemia due to enhanced renal tubular phosphate reabsorption. Fibroblast growth factor (FGF)23 was identified as a responsible factor in hypophosphatemic diseases caused by renal phosphate leak.
Objective: The objective of the study was to analyze the involvement of FGF23 in the development of tumoral calcinosis.
Design: Serum FGF23 level was evaluated in a patient with tumoral calcinosis by two kinds of ELISA: full-length assay that detects only full-length FGF23 with phosphate-lowering activity and C-terminal assay that measures full-length as well as C-terminal fragment of FGF23. FGF23 gene was analyzed by direct sequencing of PCR products, and mutant FGF23 was analyzed by Western blotting after expression in mammalian cells.
Patients: A family of tumoral calcinosis patients were studied.
Results: Serum FGF23 was extremely high when measured by C-terminal assay. In contrast, it was low normal by full-length assay. Analysis of FGF23 gene detected a serine to phenylalanine mutation in codon 129. No wild-type allele of this codon was found in the patient. The brother of the proband showed the same base change. When this mutant FGF23 was expressed in vitro, full-length and N-terminal fragments were barely detectable by Western blotting, whereas C-terminal fragment with the same molecular weight as that from wild-type FGF23 could be detected.
Conclusion: The production and serum level of C-terminal fragment of FGF23 are increased in this patient with tumoral calcinosis. Together with the recent similar report of FGF23 mutation, impaired action of full-length FGF23 seems to result in tumoral calcinosis.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>16030159</pmid><doi>10.1210/jc.2005-0301</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0021-972X |
| ispartof | The journal of clinical endocrinology and metabolism, 2005-10, Vol.90 (10), p.5523-5527 |
| issn | 0021-972X 1945-7197 |
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| recordid | cdi_proquest_miscellaneous_68663082 |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Adult Biological and medical sciences Blotting, Western Calcinosis - etiology Calcinosis - genetics Cells, Cultured Culture Media, Conditioned DNA, Antisense - genetics DNA, Complementary - biosynthesis DNA, Complementary - genetics Endocrinopathies Enzyme-Linked Immunosorbent Assay Female Fibroblast Growth Factors - genetics Fundamental and applied biological sciences. Psychology Humans Medical sciences Molecular Weight Mutation - physiology Neoplasms - complications Neoplasms - genetics Pedigree Phosphates - metabolism Reverse Transcriptase Polymerase Chain Reaction Vertebrates: endocrinology Vitamin D - metabolism |
| title | A Novel Mutation in Fibroblast Growth Factor 23 Gene as a Cause of Tumoral Calcinosis |
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