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Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia
Sclerosteosis and Van Buchem disease are related recessive sclerosing bone dysplasias caused by alterations in the SOST gene. We tested the hypothesis that craniodiaphyseal dysplasia (CDD) (MIM 122860), an extremely rare sclerosing bone dysplasia resulting facial distortion referred to as “leontiasi...
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| Published in: | Human genetics 2011-05, Vol.129 (5), p.497-502 |
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| container_title | Human genetics |
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| creator | Kim, Su Jin Bieganski, Tadeusz Sohn, Young Bae Kozlowski, Kazimierz Semënov, Mikhail Okamoto, Nobuhiko Kim, Chi Hwa Ko, Ah-Ra Ahn, Geung Hwan Choi, Yoon-La Park, Sung Won Ki, Chang-Seok Kim, Ok-Hwa Nishimura, Gen Unger, Sheila Superti-Furga, Andrea Jin, Dong-Kyu |
| description | Sclerosteosis and Van Buchem disease are related recessive sclerosing bone dysplasias caused by alterations in the
SOST
gene. We tested the hypothesis that craniodiaphyseal dysplasia (CDD) (MIM 122860), an extremely rare sclerosing bone dysplasia resulting facial distortion referred to as “leontiasis ossea”, could also be caused by SOST mutations. We discovered mutations c.61G>A (Val21Met) and c.61G>T (Val21Leu) two children with CDD. As these mutations are located in the secretion signal of the
SOST
gene, we tested their effect on secretion by transfecting the mutant constructs into 293E cells. Intriguingly, these mutations greatly reduced the secretion of
SOST
. We conclude that CDD, the most severe form of sclerotic bone disease, is part of a spectrum of disease caused by mutations in
SOST.
Unlike the other
SOST
-related conditions, sclerosteosis and Van Buchem disease that are inherited as recessive traits seem to be caused by a dominant negative mechanism. |
| doi_str_mv | 10.1007/s00439-011-0947-3 |
| format | article |
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SOST
gene. We tested the hypothesis that craniodiaphyseal dysplasia (CDD) (MIM 122860), an extremely rare sclerosing bone dysplasia resulting facial distortion referred to as “leontiasis ossea”, could also be caused by SOST mutations. We discovered mutations c.61G>A (Val21Met) and c.61G>T (Val21Leu) two children with CDD. As these mutations are located in the secretion signal of the
SOST
gene, we tested their effect on secretion by transfecting the mutant constructs into 293E cells. Intriguingly, these mutations greatly reduced the secretion of
SOST
. We conclude that CDD, the most severe form of sclerotic bone disease, is part of a spectrum of disease caused by mutations in
SOST.
Unlike the other
SOST
-related conditions, sclerosteosis and Van Buchem disease that are inherited as recessive traits seem to be caused by a dominant negative mechanism.</description><identifier>ISSN: 0340-6717</identifier><identifier>EISSN: 1432-1203</identifier><identifier>DOI: 10.1007/s00439-011-0947-3</identifier><identifier>PMID: 21221996</identifier><identifier>CODEN: HUGEDQ</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Abnormalities, Multiple - genetics ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Bone Morphogenetic Proteins - genetics ; Child ; Classical genetics, quantitative genetics, hybrids ; Cloning ; Craniofacial Abnormalities - genetics ; Diseases of the osteoarticular system ; Dysplasia ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Function ; Genetic aspects ; Genetic Markers - genetics ; Genetics of eukaryotes. Biological and molecular evolution ; Hospitals ; Human ; Human Genetics ; Humans ; Male ; Malformations and congenital and or hereditary diseases involving bones. Joint deformations ; Maternal & child health ; Medical sciences ; Medicine ; Metabolic Diseases ; Molecular Medicine ; Mutagenesis ; Mutation ; Original Investigation ; Osteochondrodysplasias ; Patients ; Pediatrics ; Peptides ; Protein Interaction Domains and Motifs - genetics ; Protein Sorting Signals - genetics</subject><ispartof>Human genetics, 2011-05, Vol.129 (5), p.497-502</ispartof><rights>Springer-Verlag 2011</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2011 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c599t-34d8518753346ef0e72af4d1a48869f58d61772d883affd96e8dc8a48fd158a3</citedby><cites>FETCH-LOGICAL-c599t-34d8518753346ef0e72af4d1a48869f58d61772d883affd96e8dc8a48fd158a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24108351$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21221996$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Su Jin</creatorcontrib><creatorcontrib>Bieganski, Tadeusz</creatorcontrib><creatorcontrib>Sohn, Young Bae</creatorcontrib><creatorcontrib>Kozlowski, Kazimierz</creatorcontrib><creatorcontrib>Semënov, Mikhail</creatorcontrib><creatorcontrib>Okamoto, Nobuhiko</creatorcontrib><creatorcontrib>Kim, Chi Hwa</creatorcontrib><creatorcontrib>Ko, Ah-Ra</creatorcontrib><creatorcontrib>Ahn, Geung Hwan</creatorcontrib><creatorcontrib>Choi, Yoon-La</creatorcontrib><creatorcontrib>Park, Sung Won</creatorcontrib><creatorcontrib>Ki, Chang-Seok</creatorcontrib><creatorcontrib>Kim, Ok-Hwa</creatorcontrib><creatorcontrib>Nishimura, Gen</creatorcontrib><creatorcontrib>Unger, Sheila</creatorcontrib><creatorcontrib>Superti-Furga, Andrea</creatorcontrib><creatorcontrib>Jin, Dong-Kyu</creatorcontrib><title>Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia</title><title>Human genetics</title><addtitle>Hum Genet</addtitle><addtitle>Hum Genet</addtitle><description>Sclerosteosis and Van Buchem disease are related recessive sclerosing bone dysplasias caused by alterations in the
SOST
gene. We tested the hypothesis that craniodiaphyseal dysplasia (CDD) (MIM 122860), an extremely rare sclerosing bone dysplasia resulting facial distortion referred to as “leontiasis ossea”, could also be caused by SOST mutations. We discovered mutations c.61G>A (Val21Met) and c.61G>T (Val21Leu) two children with CDD. As these mutations are located in the secretion signal of the
SOST
gene, we tested their effect on secretion by transfecting the mutant constructs into 293E cells. Intriguingly, these mutations greatly reduced the secretion of
SOST
. We conclude that CDD, the most severe form of sclerotic bone disease, is part of a spectrum of disease caused by mutations in
SOST.
Unlike the other
SOST
-related conditions, sclerosteosis and Van Buchem disease that are inherited as recessive traits seem to be caused by a dominant negative mechanism.</description><subject>Abnormalities, Multiple - genetics</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bone Morphogenetic Proteins - genetics</subject><subject>Child</subject><subject>Classical genetics, quantitative genetics, hybrids</subject><subject>Cloning</subject><subject>Craniofacial Abnormalities - genetics</subject><subject>Diseases of the osteoarticular system</subject><subject>Dysplasia</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Function</subject><subject>Genetic aspects</subject><subject>Genetic Markers - genetics</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Hospitals</subject><subject>Human</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Male</subject><subject>Malformations and congenital and or hereditary diseases involving bones. Joint deformations</subject><subject>Maternal & child health</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Metabolic Diseases</subject><subject>Molecular Medicine</subject><subject>Mutagenesis</subject><subject>Mutation</subject><subject>Original Investigation</subject><subject>Osteochondrodysplasias</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Peptides</subject><subject>Protein Interaction Domains and Motifs - genetics</subject><subject>Protein Sorting Signals - genetics</subject><issn>0340-6717</issn><issn>1432-1203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNqF0l2L1DAUBuAiijuu_gBvpCgiXnTNSdI2uVwWPwYWFpy5D8cmGbO0SW1S2Pn3pjujy4giuQjkPCeHpm9RvARyAYS0HyIhnMmKAFRE8rZij4oVcEYroIQ9LlaEcVI1LbRnxbMYbwmBWtL6aXFGgVKQslkVu7U2PjnrOkwu-DLYMrqdx74czZicNqUOAzpfbm4223KY0z2LZT7BOYWYi_1CnEefym5C74J2OH7fR7NU9nHsMTp8Xjyx2Efz4rifF9tPH7dXX6rrm8_rq8vrqqulTBXjWtQg2pox3hhLTEvRcg3IhWikrYVuoG2pFoKhtVo2RuhO5KrVUAtk58W7w7XjFH7MJiY1uNiZvkdvwhyVJJQ1wNvmv1LkQRJos8jXf8jbME_5ie4Rk5RzkdGbA9phb5TzNqQJu-VKdckaLmsJArK6-IvKS5vBdcEb6_L5ScP7k4ZskrlLO5xjVOvN11MLB9tNIcbJWDVObsBpr4CoJS_qkBeV86KWvCiWe14dv23-Nhj9u-NXQDJ4ewQYO-xt_sGdiw-OAxGsXobTg4u55Hdmenikf0__CQw91Xg</recordid><startdate>20110501</startdate><enddate>20110501</enddate><creator>Kim, Su Jin</creator><creator>Bieganski, Tadeusz</creator><creator>Sohn, Young Bae</creator><creator>Kozlowski, Kazimierz</creator><creator>Semënov, Mikhail</creator><creator>Okamoto, Nobuhiko</creator><creator>Kim, Chi Hwa</creator><creator>Ko, Ah-Ra</creator><creator>Ahn, Geung Hwan</creator><creator>Choi, Yoon-La</creator><creator>Park, Sung Won</creator><creator>Ki, Chang-Seok</creator><creator>Kim, Ok-Hwa</creator><creator>Nishimura, Gen</creator><creator>Unger, Sheila</creator><creator>Superti-Furga, Andrea</creator><creator>Jin, Dong-Kyu</creator><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</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>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20110501</creationdate><title>Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia</title><author>Kim, Su Jin ; Bieganski, Tadeusz ; Sohn, Young Bae ; Kozlowski, Kazimierz ; Semënov, Mikhail ; Okamoto, Nobuhiko ; Kim, Chi Hwa ; Ko, Ah-Ra ; Ahn, Geung Hwan ; Choi, Yoon-La ; Park, Sung Won ; Ki, Chang-Seok ; Kim, Ok-Hwa ; Nishimura, Gen ; Unger, Sheila ; Superti-Furga, Andrea ; Jin, Dong-Kyu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c599t-34d8518753346ef0e72af4d1a48869f58d61772d883affd96e8dc8a48fd158a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Abnormalities, Multiple - genetics</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Bone Morphogenetic Proteins - genetics</topic><topic>Child</topic><topic>Classical genetics, quantitative genetics, hybrids</topic><topic>Cloning</topic><topic>Craniofacial Abnormalities - genetics</topic><topic>Diseases of the osteoarticular system</topic><topic>Dysplasia</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Function</topic><topic>Genetic aspects</topic><topic>Genetic Markers - genetics</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Hospitals</topic><topic>Human</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Male</topic><topic>Malformations and congenital and or hereditary diseases involving bones. 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Academic</collection><jtitle>Human genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Su Jin</au><au>Bieganski, Tadeusz</au><au>Sohn, Young Bae</au><au>Kozlowski, Kazimierz</au><au>Semënov, Mikhail</au><au>Okamoto, Nobuhiko</au><au>Kim, Chi Hwa</au><au>Ko, Ah-Ra</au><au>Ahn, Geung Hwan</au><au>Choi, Yoon-La</au><au>Park, Sung Won</au><au>Ki, Chang-Seok</au><au>Kim, Ok-Hwa</au><au>Nishimura, Gen</au><au>Unger, Sheila</au><au>Superti-Furga, Andrea</au><au>Jin, Dong-Kyu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia</atitle><jtitle>Human genetics</jtitle><stitle>Hum Genet</stitle><addtitle>Hum Genet</addtitle><date>2011-05-01</date><risdate>2011</risdate><volume>129</volume><issue>5</issue><spage>497</spage><epage>502</epage><pages>497-502</pages><issn>0340-6717</issn><eissn>1432-1203</eissn><coden>HUGEDQ</coden><notes>ObjectType-Case Study-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-4</notes><notes>content type line 23</notes><notes>ObjectType-Report-1</notes><notes>ObjectType-Article-3</notes><notes>ObjectType-Article-2</notes><notes>ObjectType-Feature-1</notes><abstract>Sclerosteosis and Van Buchem disease are related recessive sclerosing bone dysplasias caused by alterations in the
SOST
gene. We tested the hypothesis that craniodiaphyseal dysplasia (CDD) (MIM 122860), an extremely rare sclerosing bone dysplasia resulting facial distortion referred to as “leontiasis ossea”, could also be caused by SOST mutations. We discovered mutations c.61G>A (Val21Met) and c.61G>T (Val21Leu) two children with CDD. As these mutations are located in the secretion signal of the
SOST
gene, we tested their effect on secretion by transfecting the mutant constructs into 293E cells. Intriguingly, these mutations greatly reduced the secretion of
SOST
. We conclude that CDD, the most severe form of sclerotic bone disease, is part of a spectrum of disease caused by mutations in
SOST.
Unlike the other
SOST
-related conditions, sclerosteosis and Van Buchem disease that are inherited as recessive traits seem to be caused by a dominant negative mechanism.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>21221996</pmid><doi>10.1007/s00439-011-0947-3</doi><tpages>6</tpages></addata></record> |
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| ispartof | Human genetics, 2011-05, Vol.129 (5), p.497-502 |
| issn | 0340-6717 1432-1203 |
| language | eng |
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| source | Springer Link |
| subjects | Abnormalities, Multiple - genetics Biological and medical sciences Biomedical and Life Sciences Biomedicine Bone Morphogenetic Proteins - genetics Child Classical genetics, quantitative genetics, hybrids Cloning Craniofacial Abnormalities - genetics Diseases of the osteoarticular system Dysplasia Female Fundamental and applied biological sciences. Psychology Gene Function Genetic aspects Genetic Markers - genetics Genetics of eukaryotes. Biological and molecular evolution Hospitals Human Human Genetics Humans Male Malformations and congenital and or hereditary diseases involving bones. Joint deformations Maternal & child health Medical sciences Medicine Metabolic Diseases Molecular Medicine Mutagenesis Mutation Original Investigation Osteochondrodysplasias Patients Pediatrics Peptides Protein Interaction Domains and Motifs - genetics Protein Sorting Signals - genetics |
| title | Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia |
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