A deleterious founder mutation in the BMPER gene causes diaphanospondylodysostosis (DSD)
Diaphonospondylodysostosis (DSD) is a rare, recessively inherited, lethal skeletal dysplasia, characterized by severe spinal ossification, segmentation defects, and renal cystic dysplasia with nephrogenic rests. We hereby present three affected individuals: two children and a fetus from two unrelate...
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| Veröffentlicht in: | American journal of medical genetics. Part A 2011-11, Vol.155 (11), p.2801-2806 |
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| creator | Ben‐Neriah, Ziva Michaelson‐Cohen, Rachel Inbar‐Feigenberg, Michal Nadjari, Michael Zeligson, Sharon Shaag, Avraham Zenvirt, Shamir Elpeleg, Orly Levy‐Lahad, Ephrat |
| description | Diaphonospondylodysostosis (DSD) is a rare, recessively inherited, lethal skeletal dysplasia, characterized by severe spinal ossification, segmentation defects, and renal cystic dysplasia with nephrogenic rests. We hereby present three affected individuals: two children and a fetus from two unrelated East Jerusalem Arab‐Muslim families. Whereas most fetuses die in utero or perinatally, one of the children survived to 15 months. Homozygosity mapping in the two families demonstrated a single common 3.87 Mb region on chromosome 7, ruling out previously known spondylocostal/spondylothoracic dysostosis loci. The 15 protein coding genes in the region were prioritized, and some were sequenced. A single, novel deleterious mutation, Q104X, was detected in the bone morphogenetic protein‐binding endothelial regulator protein (BMPER) gene, recently reported to be mutated in other DSD patients [Funari et al., 2010]. The novel mutation we identified is an ancestral founder allele, as evidenced by a shared 440 SNP haplotype, and its frequency in the general Arab population is estimated to be |
| doi_str_mv | 10.1002/ajmg.a.34240 |
| format | Article |
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We hereby present three affected individuals: two children and a fetus from two unrelated East Jerusalem Arab‐Muslim families. Whereas most fetuses die in utero or perinatally, one of the children survived to 15 months. Homozygosity mapping in the two families demonstrated a single common 3.87 Mb region on chromosome 7, ruling out previously known spondylocostal/spondylothoracic dysostosis loci. The 15 protein coding genes in the region were prioritized, and some were sequenced. A single, novel deleterious mutation, Q104X, was detected in the bone morphogenetic protein‐binding endothelial regulator protein (BMPER) gene, recently reported to be mutated in other DSD patients [Funari et al., 2010]. The novel mutation we identified is an ancestral founder allele, as evidenced by a shared 440 SNP haplotype, and its frequency in the general Arab population is estimated to be <1:123. Our findings confirm loss of BMPER function as a cause of axial versus appendicular skeletal defects, and suggest that less deleterious mutations may be involved in milder axial skeleton abnormalities. © 2011 Wiley Periodicals, Inc.</description><identifier>ISSN: 1552-4825</identifier><identifier>ISSN: 1552-4833</identifier><identifier>EISSN: 1552-4833</identifier><identifier>DOI: 10.1002/ajmg.a.34240</identifier><identifier>PMID: 21990102</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Arabs - genetics ; Biological and medical sciences ; BMPER gene ; Bone (axial) ; Bone dysplasia ; Carrier Proteins - genetics ; Children ; chromosome 7 ; Chromosome Mapping ; Chromosomes, Human, Pair 17 - genetics ; Classical genetics, quantitative genetics, hybrids ; diaphonospondylodysostosis ; Dysostosis ; Female ; Fetuses ; Founder Effect ; Fundamental and applied biological sciences. Psychology ; Gene Frequency ; Gene mapping ; Genetic Counseling ; Genetics of eukaryotes. Biological and molecular evolution ; Haplotypes ; homozygosity mapping ; Homozygote ; Human ; Humans ; Infant ; Infant, Newborn ; Kidney ; Medical genetics ; Medical sciences ; Mutation ; Nuchal Translucency Measurement ; Ossification ; Pedigree ; Polymorphism, Single Nucleotide ; Population genetics ; Population genetics, reproduction patterns ; Pregnancy ; Pregnancy Trimester, Second - genetics ; Radiography ; Segmentation ; Single-nucleotide polymorphism ; skeletal dysplasia ; Skeleton ; Spondylosis - diagnosis ; Spondylosis - diagnostic imaging ; Spondylosis - genetics</subject><ispartof>American journal of medical genetics. 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Part A</title><addtitle>Am J Med Genet A</addtitle><description>Diaphonospondylodysostosis (DSD) is a rare, recessively inherited, lethal skeletal dysplasia, characterized by severe spinal ossification, segmentation defects, and renal cystic dysplasia with nephrogenic rests. We hereby present three affected individuals: two children and a fetus from two unrelated East Jerusalem Arab‐Muslim families. Whereas most fetuses die in utero or perinatally, one of the children survived to 15 months. Homozygosity mapping in the two families demonstrated a single common 3.87 Mb region on chromosome 7, ruling out previously known spondylocostal/spondylothoracic dysostosis loci. The 15 protein coding genes in the region were prioritized, and some were sequenced. A single, novel deleterious mutation, Q104X, was detected in the bone morphogenetic protein‐binding endothelial regulator protein (BMPER) gene, recently reported to be mutated in other DSD patients [Funari et al., 2010]. The novel mutation we identified is an ancestral founder allele, as evidenced by a shared 440 SNP haplotype, and its frequency in the general Arab population is estimated to be <1:123. Our findings confirm loss of BMPER function as a cause of axial versus appendicular skeletal defects, and suggest that less deleterious mutations may be involved in milder axial skeleton abnormalities. © 2011 Wiley Periodicals, Inc.</description><subject>Arabs - genetics</subject><subject>Biological and medical sciences</subject><subject>BMPER gene</subject><subject>Bone (axial)</subject><subject>Bone dysplasia</subject><subject>Carrier Proteins - genetics</subject><subject>Children</subject><subject>chromosome 7</subject><subject>Chromosome Mapping</subject><subject>Chromosomes, Human, Pair 17 - genetics</subject><subject>Classical genetics, quantitative genetics, hybrids</subject><subject>diaphonospondylodysostosis</subject><subject>Dysostosis</subject><subject>Female</subject><subject>Fetuses</subject><subject>Founder Effect</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Frequency</subject><subject>Gene mapping</subject><subject>Genetic Counseling</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Haplotypes</subject><subject>homozygosity mapping</subject><subject>Homozygote</subject><subject>Human</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Kidney</subject><subject>Medical genetics</subject><subject>Medical sciences</subject><subject>Mutation</subject><subject>Nuchal Translucency Measurement</subject><subject>Ossification</subject><subject>Pedigree</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population genetics</subject><subject>Population genetics, reproduction patterns</subject><subject>Pregnancy</subject><subject>Pregnancy Trimester, Second - genetics</subject><subject>Radiography</subject><subject>Segmentation</subject><subject>Single-nucleotide polymorphism</subject><subject>skeletal dysplasia</subject><subject>Skeleton</subject><subject>Spondylosis - diagnosis</subject><subject>Spondylosis - diagnostic imaging</subject><subject>Spondylosis - genetics</subject><issn>1552-4825</issn><issn>1552-4833</issn><issn>1552-4833</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90c1rFDEYBvAgiq3Vm2cJiFjBXfM9k-Pa1qq0KH6At5BJ3mmzzCRrMoPsf2_qrhU89BDeHH48Ly8PQk8pWVJC2Bu7Hq-WdskFE-QeOqRSsoVoOb9_-2fyAD0qZU0IJ7JRD9EBo1oTStgh-rHCHgaYIIc0F9ynOXrIeJwnO4UUcYh4ugb89vLz2Rd8BRGws3OBgn2wm2sbU9mk6LdD8tuSypRKKPj49Ovpq8foQW-HAk_28wh9f3f27eT94uLT-YeT1cXCCSbJwveiFdYLRWUHjlhen1PAWk8odc53VjZOc-8kdZIB7XnrNBVdp1VjNdf8CL3c5W5y-jlDmcwYioNhsBHqRUYTojjXrKny-E5JCW100wjWVvr8P7pOc471DkMbpSpknFX1eqdcTqVk6M0mh9HmbY0yN92Ym26MNX-6qfzZPnTuRvC3-G8ZFbzYA1ucHfpsowvlnxOqVZSq6vjO_QoDbO9calYfL893638DCi6mWQ</recordid><startdate>201111</startdate><enddate>201111</enddate><creator>Ben‐Neriah, Ziva</creator><creator>Michaelson‐Cohen, Rachel</creator><creator>Inbar‐Feigenberg, Michal</creator><creator>Nadjari, Michael</creator><creator>Zeligson, Sharon</creator><creator>Shaag, Avraham</creator><creator>Zenvirt, Shamir</creator><creator>Elpeleg, Orly</creator><creator>Levy‐Lahad, Ephrat</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</general><general>Wiley Subscription Services, Inc</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>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201111</creationdate><title>A deleterious founder mutation in the BMPER gene causes diaphanospondylodysostosis (DSD)</title><author>Ben‐Neriah, Ziva ; Michaelson‐Cohen, Rachel ; Inbar‐Feigenberg, Michal ; Nadjari, Michael ; Zeligson, Sharon ; Shaag, Avraham ; Zenvirt, Shamir ; Elpeleg, Orly ; Levy‐Lahad, Ephrat</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4250-df484ad4615bec0a3c0ac6e28d011ccdba57c93dc51c52e1f38c914bb967a9393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Arabs - genetics</topic><topic>Biological and medical sciences</topic><topic>BMPER gene</topic><topic>Bone (axial)</topic><topic>Bone dysplasia</topic><topic>Carrier Proteins - genetics</topic><topic>Children</topic><topic>chromosome 7</topic><topic>Chromosome Mapping</topic><topic>Chromosomes, Human, Pair 17 - genetics</topic><topic>Classical genetics, quantitative genetics, hybrids</topic><topic>diaphonospondylodysostosis</topic><topic>Dysostosis</topic><topic>Female</topic><topic>Fetuses</topic><topic>Founder Effect</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Frequency</topic><topic>Gene mapping</topic><topic>Genetic Counseling</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Haplotypes</topic><topic>homozygosity mapping</topic><topic>Homozygote</topic><topic>Human</topic><topic>Humans</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>Kidney</topic><topic>Medical genetics</topic><topic>Medical sciences</topic><topic>Mutation</topic><topic>Nuchal Translucency Measurement</topic><topic>Ossification</topic><topic>Pedigree</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population genetics</topic><topic>Population genetics, reproduction patterns</topic><topic>Pregnancy</topic><topic>Pregnancy Trimester, Second - genetics</topic><topic>Radiography</topic><topic>Segmentation</topic><topic>Single-nucleotide polymorphism</topic><topic>skeletal dysplasia</topic><topic>Skeleton</topic><topic>Spondylosis - diagnosis</topic><topic>Spondylosis - diagnostic imaging</topic><topic>Spondylosis - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ben‐Neriah, Ziva</creatorcontrib><creatorcontrib>Michaelson‐Cohen, Rachel</creatorcontrib><creatorcontrib>Inbar‐Feigenberg, Michal</creatorcontrib><creatorcontrib>Nadjari, Michael</creatorcontrib><creatorcontrib>Zeligson, Sharon</creatorcontrib><creatorcontrib>Shaag, Avraham</creatorcontrib><creatorcontrib>Zenvirt, Shamir</creatorcontrib><creatorcontrib>Elpeleg, Orly</creatorcontrib><creatorcontrib>Levy‐Lahad, Ephrat</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>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of medical genetics. Part A</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ben‐Neriah, Ziva</au><au>Michaelson‐Cohen, Rachel</au><au>Inbar‐Feigenberg, Michal</au><au>Nadjari, Michael</au><au>Zeligson, Sharon</au><au>Shaag, Avraham</au><au>Zenvirt, Shamir</au><au>Elpeleg, Orly</au><au>Levy‐Lahad, Ephrat</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A deleterious founder mutation in the BMPER gene causes diaphanospondylodysostosis (DSD)</atitle><jtitle>American journal of medical genetics. Part A</jtitle><addtitle>Am J Med Genet A</addtitle><date>2011-11</date><risdate>2011</risdate><volume>155</volume><issue>11</issue><spage>2801</spage><epage>2806</epage><pages>2801-2806</pages><issn>1552-4825</issn><issn>1552-4833</issn><eissn>1552-4833</eissn><abstract>Diaphonospondylodysostosis (DSD) is a rare, recessively inherited, lethal skeletal dysplasia, characterized by severe spinal ossification, segmentation defects, and renal cystic dysplasia with nephrogenic rests. We hereby present three affected individuals: two children and a fetus from two unrelated East Jerusalem Arab‐Muslim families. Whereas most fetuses die in utero or perinatally, one of the children survived to 15 months. Homozygosity mapping in the two families demonstrated a single common 3.87 Mb region on chromosome 7, ruling out previously known spondylocostal/spondylothoracic dysostosis loci. The 15 protein coding genes in the region were prioritized, and some were sequenced. A single, novel deleterious mutation, Q104X, was detected in the bone morphogenetic protein‐binding endothelial regulator protein (BMPER) gene, recently reported to be mutated in other DSD patients [Funari et al., 2010]. The novel mutation we identified is an ancestral founder allele, as evidenced by a shared 440 SNP haplotype, and its frequency in the general Arab population is estimated to be <1:123. Our findings confirm loss of BMPER function as a cause of axial versus appendicular skeletal defects, and suggest that less deleterious mutations may be involved in milder axial skeleton abnormalities. © 2011 Wiley Periodicals, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21990102</pmid><doi>10.1002/ajmg.a.34240</doi><tpages>6</tpages></addata></record> |
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| subjects | Arabs - genetics Biological and medical sciences BMPER gene Bone (axial) Bone dysplasia Carrier Proteins - genetics Children chromosome 7 Chromosome Mapping Chromosomes, Human, Pair 17 - genetics Classical genetics, quantitative genetics, hybrids diaphonospondylodysostosis Dysostosis Female Fetuses Founder Effect Fundamental and applied biological sciences. Psychology Gene Frequency Gene mapping Genetic Counseling Genetics of eukaryotes. Biological and molecular evolution Haplotypes homozygosity mapping Homozygote Human Humans Infant Infant, Newborn Kidney Medical genetics Medical sciences Mutation Nuchal Translucency Measurement Ossification Pedigree Polymorphism, Single Nucleotide Population genetics Population genetics, reproduction patterns Pregnancy Pregnancy Trimester, Second - genetics Radiography Segmentation Single-nucleotide polymorphism skeletal dysplasia Skeleton Spondylosis - diagnosis Spondylosis - diagnostic imaging Spondylosis - genetics |
| title | A deleterious founder mutation in the BMPER gene causes diaphanospondylodysostosis (DSD) |
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