The <it>ADAMTS18 </it>gene is responsible for autosomal recessive early onset severe retinal dystrophy
<p>Abstract</p> <p>Background</p> <p>Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mut...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2013-01-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | http://www.ojrd.com/content/8/1/16 |
| _version_ | 1818235667926220800 |
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| author | Peluso Ivana Conte Ivan Testa Francesco Dharmalingam Gopuraja Pizzo Mariateresa Collin Rob WJ Meola Nicola Barbato Sara Mutarelli Margherita Ziviello Carmela Barbarulo Anna Maria Nigro Vincenzo Melone Mariarosa AB Simonelli Francesca Banfi Sandro |
| author_facet | Peluso Ivana Conte Ivan Testa Francesco Dharmalingam Gopuraja Pizzo Mariateresa Collin Rob WJ Meola Nicola Barbato Sara Mutarelli Margherita Ziviello Carmela Barbarulo Anna Maria Nigro Vincenzo Melone Mariarosa AB Simonelli Francesca Banfi Sandro |
| author_sort | Peluso Ivana |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy in a patient carrying no previously described mutations in known genes.</p> <p>Methods</p> <p>An integrated strategy including homozygosity mapping and whole exome sequencing was used to identify the responsible mutation. Functional tests were performed in the medaka fish (<it>Oryzias latipes</it>) model organism to gain further insight into the pathogenic role of the <it>ADAMTS18</it> gene in eye and central nervous system (CNS) dysfunction.</p> <p>Results</p> <p>This study identified, in the analyzed patient, a homozygous missense mutation in the <it>ADAMTS18</it> gene, which was recently linked to Knobloch syndrome, a rare developmental disorder that affects the eye and the occipital skull. <it>In vivo</it> gene knockdown performed in medaka fish confirmed both that the mutation has a pathogenic role and that the inactivation of this gene has a deleterious effect on photoreceptor cell function.</p> <p>Conclusion</p> <p>This study reveals that mutations in the <it>ADAMTS18</it> gene can cause a broad phenotypic spectrum of eye disorders and contribute to shed further light on the complexity of retinal diseases.</p> |
| first_indexed | 2024-12-12T11:57:37Z |
| format | Article |
| id | doaj.art-82d4517bd0604c5883d454eebadf56b5 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-12T11:57:37Z |
| publishDate | 2013-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-82d4517bd0604c5883d454eebadf56b52022-12-22T00:25:11ZengBMCOrphanet Journal of Rare Diseases1750-11722013-01-01811610.1186/1750-1172-8-16The <it>ADAMTS18 </it>gene is responsible for autosomal recessive early onset severe retinal dystrophyPeluso IvanaConte IvanTesta FrancescoDharmalingam GopurajaPizzo MariateresaCollin Rob WJMeola NicolaBarbato SaraMutarelli MargheritaZiviello CarmelaBarbarulo Anna MariaNigro VincenzoMelone Mariarosa ABSimonelli FrancescaBanfi Sandro<p>Abstract</p> <p>Background</p> <p>Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy in a patient carrying no previously described mutations in known genes.</p> <p>Methods</p> <p>An integrated strategy including homozygosity mapping and whole exome sequencing was used to identify the responsible mutation. Functional tests were performed in the medaka fish (<it>Oryzias latipes</it>) model organism to gain further insight into the pathogenic role of the <it>ADAMTS18</it> gene in eye and central nervous system (CNS) dysfunction.</p> <p>Results</p> <p>This study identified, in the analyzed patient, a homozygous missense mutation in the <it>ADAMTS18</it> gene, which was recently linked to Knobloch syndrome, a rare developmental disorder that affects the eye and the occipital skull. <it>In vivo</it> gene knockdown performed in medaka fish confirmed both that the mutation has a pathogenic role and that the inactivation of this gene has a deleterious effect on photoreceptor cell function.</p> <p>Conclusion</p> <p>This study reveals that mutations in the <it>ADAMTS18</it> gene can cause a broad phenotypic spectrum of eye disorders and contribute to shed further light on the complexity of retinal diseases.</p>http://www.ojrd.com/content/8/1/16Inherited retinal dystrophiesADAMTS18ExomeHomozygosity mappingMedaka fishKnobloch syndrome |
| spellingShingle | Peluso Ivana Conte Ivan Testa Francesco Dharmalingam Gopuraja Pizzo Mariateresa Collin Rob WJ Meola Nicola Barbato Sara Mutarelli Margherita Ziviello Carmela Barbarulo Anna Maria Nigro Vincenzo Melone Mariarosa AB Simonelli Francesca Banfi Sandro The <it>ADAMTS18 </it>gene is responsible for autosomal recessive early onset severe retinal dystrophy Orphanet Journal of Rare Diseases Inherited retinal dystrophies ADAMTS18 Exome Homozygosity mapping Medaka fish Knobloch syndrome |
| title | The <it>ADAMTS18 </it>gene is responsible for autosomal recessive early onset severe retinal dystrophy |
| title_full | The <it>ADAMTS18 </it>gene is responsible for autosomal recessive early onset severe retinal dystrophy |
| title_fullStr | The <it>ADAMTS18 </it>gene is responsible for autosomal recessive early onset severe retinal dystrophy |
| title_full_unstemmed | The <it>ADAMTS18 </it>gene is responsible for autosomal recessive early onset severe retinal dystrophy |
| title_short | The <it>ADAMTS18 </it>gene is responsible for autosomal recessive early onset severe retinal dystrophy |
| title_sort | it adamts18 it gene is responsible for autosomal recessive early onset severe retinal dystrophy |
| topic | Inherited retinal dystrophies ADAMTS18 Exome Homozygosity mapping Medaka fish Knobloch syndrome |
| url | http://www.ojrd.com/content/8/1/16 |
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