A Homozygous Mutation in ADAMTSL4 Causes Autosomal-Recessive Isolated Ectopia Lentis
Ectopia lentis is a genetically heterogeneous condition that is characterized by the subluxation of the lens resulting from the disruption of the zonular fibers. Patients with ectopia lentis commonly present with a marked loss in visual acuity in addition to a number of possibly accompanying ocular...
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| Veröffentlicht in: | American journal of human genetics 2009-02, Vol.84 (2), p.274-278 |
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| creator | Ahram, Dina Sato, T. Shawn Kohilan, Abdulghani Tayeh, Marwan Chen, Shan Leal, Suzanne Al-Salem, Mahmoud El-Shanti, Hatem |
| description | Ectopia lentis is a genetically heterogeneous condition that is characterized by the subluxation of the lens resulting from the disruption of the zonular fibers. Patients with ectopia lentis commonly present with a marked loss in visual acuity in addition to a number of possibly accompanying ocular complications including cataract, myopia, and retinal detachment. We here describe an isolated form of ectopia lentis in a large inbred family that shows autosomal-recessive inheritance. We map the ectopia lentis locus in this family to the pericentromeric region on chromosome 1 (1p13.2-q21.1). The linkage region contains well more than 60 genes. Mutation screening of four candidate genes revealed a homozygous nonsense mutation in exon 11 of ADAMTSL4 (p.Y595X; c.1785T→G) in all affected individuals that is absent in 380 control chromosomes. The mutation would result in a truncated protein of half the original length, if the mRNA escapes nonsense-mediated decay. We conclude that mutations in ADAMTSL4 are responsible for autosomal-recessive simple ectopia lentis and that ADAMTS-like4 plays a role in the development and/or integrity of the zonular fibers. |
| doi_str_mv | 10.1016/j.ajhg.2009.01.007 |
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Shawn ; Kohilan, Abdulghani ; Tayeh, Marwan ; Chen, Shan ; Leal, Suzanne ; Al-Salem, Mahmoud ; El-Shanti, Hatem</creator><creatorcontrib>Ahram, Dina ; Sato, T. Shawn ; Kohilan, Abdulghani ; Tayeh, Marwan ; Chen, Shan ; Leal, Suzanne ; Al-Salem, Mahmoud ; El-Shanti, Hatem</creatorcontrib><description>Ectopia lentis is a genetically heterogeneous condition that is characterized by the subluxation of the lens resulting from the disruption of the zonular fibers. Patients with ectopia lentis commonly present with a marked loss in visual acuity in addition to a number of possibly accompanying ocular complications including cataract, myopia, and retinal detachment. We here describe an isolated form of ectopia lentis in a large inbred family that shows autosomal-recessive inheritance. We map the ectopia lentis locus in this family to the pericentromeric region on chromosome 1 (1p13.2-q21.1). The linkage region contains well more than 60 genes. Mutation screening of four candidate genes revealed a homozygous nonsense mutation in exon 11 of ADAMTSL4 (p.Y595X; c.1785T→G) in all affected individuals that is absent in 380 control chromosomes. The mutation would result in a truncated protein of half the original length, if the mRNA escapes nonsense-mediated decay. We conclude that mutations in ADAMTSL4 are responsible for autosomal-recessive simple ectopia lentis and that ADAMTS-like4 plays a role in the development and/or integrity of the zonular fibers.</description><identifier>ISSN: 0002-9297</identifier><identifier>EISSN: 1537-6605</identifier><identifier>DOI: 10.1016/j.ajhg.2009.01.007</identifier><identifier>PMID: 19200529</identifier><identifier>CODEN: AJHGAG</identifier><language>eng</language><publisher>Cambridge, MA: Elsevier Inc</publisher><subject>ADAMTS Proteins ; Base Sequence ; Biological and medical sciences ; Chromosomes ; Consanguinity ; Ectopia Lentis - genetics ; Eye diseases ; Eyes & eyesight ; Female ; Fundamental and applied biological sciences. Psychology ; General aspects. Genetic counseling ; Genes ; Genes, Recessive ; Genetic Markers ; Genetics of eukaryotes. Biological and molecular evolution ; Homozygote ; Humans ; Jordan ; Lod Score ; Male ; Medical genetics ; Medical sciences ; Molecular and cellular biology ; Mutation ; Pedigree ; Polymorphism, Single Nucleotide ; Proteins ; Ribonucleic acid ; RNA ; Siblings ; Thrombospondins - genetics</subject><ispartof>American journal of human genetics, 2009-02, Vol.84 (2), p.274-278</ispartof><rights>2009 The American Society of Human Genetics</rights><rights>2009 INIST-CNRS</rights><rights>Copyright University of Chicago, acting through its Press Feb 13, 2009</rights><rights>2009 The American Society of Human Genetics. Published by Elsevier Ltd. 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Shawn</creatorcontrib><creatorcontrib>Kohilan, Abdulghani</creatorcontrib><creatorcontrib>Tayeh, Marwan</creatorcontrib><creatorcontrib>Chen, Shan</creatorcontrib><creatorcontrib>Leal, Suzanne</creatorcontrib><creatorcontrib>Al-Salem, Mahmoud</creatorcontrib><creatorcontrib>El-Shanti, Hatem</creatorcontrib><title>A Homozygous Mutation in ADAMTSL4 Causes Autosomal-Recessive Isolated Ectopia Lentis</title><title>American journal of human genetics</title><addtitle>Am J Hum Genet</addtitle><description>Ectopia lentis is a genetically heterogeneous condition that is characterized by the subluxation of the lens resulting from the disruption of the zonular fibers. Patients with ectopia lentis commonly present with a marked loss in visual acuity in addition to a number of possibly accompanying ocular complications including cataract, myopia, and retinal detachment. We here describe an isolated form of ectopia lentis in a large inbred family that shows autosomal-recessive inheritance. We map the ectopia lentis locus in this family to the pericentromeric region on chromosome 1 (1p13.2-q21.1). The linkage region contains well more than 60 genes. Mutation screening of four candidate genes revealed a homozygous nonsense mutation in exon 11 of ADAMTSL4 (p.Y595X; c.1785T→G) in all affected individuals that is absent in 380 control chromosomes. The mutation would result in a truncated protein of half the original length, if the mRNA escapes nonsense-mediated decay. We conclude that mutations in ADAMTSL4 are responsible for autosomal-recessive simple ectopia lentis and that ADAMTS-like4 plays a role in the development and/or integrity of the zonular fibers.</description><subject>ADAMTS Proteins</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Chromosomes</subject><subject>Consanguinity</subject><subject>Ectopia Lentis - genetics</subject><subject>Eye diseases</subject><subject>Eyes & eyesight</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>General aspects. Genetic counseling</subject><subject>Genes</subject><subject>Genes, Recessive</subject><subject>Genetic Markers</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Homozygote</subject><subject>Humans</subject><subject>Jordan</subject><subject>Lod Score</subject><subject>Male</subject><subject>Medical genetics</subject><subject>Medical sciences</subject><subject>Molecular and cellular biology</subject><subject>Mutation</subject><subject>Pedigree</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Proteins</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Siblings</subject><subject>Thrombospondins - genetics</subject><issn>0002-9297</issn><issn>1537-6605</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kV-L1DAUxYMo7jj6BXyQIuhb601qkwZEKOPqLswi6PgcMuntbErbzCbpwPrpzTDD-ufBl-Qhv3Nz7jmEvKRQUKD8XV_o_nZXMABZAC0AxCOyoFUpcs6hekwWAMByyaS4IM9C6AEoraF8Si6oTKKKyQXZNNmVG93P-52bQ3YzRx2tmzI7Zc2n5mbzff0-W-k5YMiaObrgRj3k39BgCPaA2XVwg47YZpcmur3V2RqnaMNz8qTTQ8AX53tJfny-3Kyu8vXXL9erZp2bSvCYG0FpWQnWgdFMoDQdh5ohF0glcI6mAqQtCNF1WshkuSu3DES1FRw4aF0uycfT3P28HbE16XOvB7X3dtT-Xjlt1d8vk71VO3dQjPM6BZAGvD0P8O5uxhDVaIPBYdATpjwU55LWsuYJfP0P2LvZT2k5xajkZVlzmSB2gox3IXjsHpxQUMfGVK-OjaljYwqoSo0l0as_d_gtOVeUgDdnQAejh87rydjwwLGUYS3TsSQfThymxA8WvQrG4mSwtR5NVK2z__PxC8kLs24</recordid><startdate>20090213</startdate><enddate>20090213</enddate><creator>Ahram, Dina</creator><creator>Sato, T. 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We here describe an isolated form of ectopia lentis in a large inbred family that shows autosomal-recessive inheritance. We map the ectopia lentis locus in this family to the pericentromeric region on chromosome 1 (1p13.2-q21.1). The linkage region contains well more than 60 genes. Mutation screening of four candidate genes revealed a homozygous nonsense mutation in exon 11 of ADAMTSL4 (p.Y595X; c.1785T→G) in all affected individuals that is absent in 380 control chromosomes. The mutation would result in a truncated protein of half the original length, if the mRNA escapes nonsense-mediated decay. We conclude that mutations in ADAMTSL4 are responsible for autosomal-recessive simple ectopia lentis and that ADAMTS-like4 plays a role in the development and/or integrity of the zonular fibers.</abstract><cop>Cambridge, MA</cop><pub>Elsevier Inc</pub><pmid>19200529</pmid><doi>10.1016/j.ajhg.2009.01.007</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | ADAMTS Proteins Base Sequence Biological and medical sciences Chromosomes Consanguinity Ectopia Lentis - genetics Eye diseases Eyes & eyesight Female Fundamental and applied biological sciences. Psychology General aspects. Genetic counseling Genes Genes, Recessive Genetic Markers Genetics of eukaryotes. Biological and molecular evolution Homozygote Humans Jordan Lod Score Male Medical genetics Medical sciences Molecular and cellular biology Mutation Pedigree Polymorphism, Single Nucleotide Proteins Ribonucleic acid RNA Siblings Thrombospondins - genetics |
| title | A Homozygous Mutation in ADAMTSL4 Causes Autosomal-Recessive Isolated Ectopia Lentis |
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