Loss of ALDH18A1 function is associated with a cellular lipid droplet phenotype suggesting a link between autosomal recessive cutis laxa type 3A and Warburg Micro syndrome
Abstract Autosomal recessive cutis laxa type 3A is caused by mutations in ALDH18A1, a gene encoding the mitochondrial enzyme ∆1‐pyrroline‐5‐carboxylate synthase (P5CS). It is a rare disorder with only six pathogenic mutations and 10 affected individuals from five families previously described in the...
| 出版年: | Molecular Genetics & Genomic Medicine |
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| 主要な著者: | , , , , , , , |
| フォーマット: | 論文 |
| 言語: | 英語 |
| 出版事項: |
Wiley
2014-07-01
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| 主題: | |
| オンライン･アクセス: | https://doi.org/10.1002/mgg3.70 |
| _version_ | 1849715695952068608 |
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| author | Mark T. Handley André Mégarbané Alison M. Meynert Stephen Brown Elisabeth Freyer Martin S. Taylor Ian J. Jackson Irene A. Aligianis |
| author_facet | Mark T. Handley André Mégarbané Alison M. Meynert Stephen Brown Elisabeth Freyer Martin S. Taylor Ian J. Jackson Irene A. Aligianis |
| author_sort | Mark T. Handley |
| collection | DOAJ |
| container_title | Molecular Genetics & Genomic Medicine |
| description | Abstract Autosomal recessive cutis laxa type 3A is caused by mutations in ALDH18A1, a gene encoding the mitochondrial enzyme ∆1‐pyrroline‐5‐carboxylate synthase (P5CS). It is a rare disorder with only six pathogenic mutations and 10 affected individuals from five families previously described in the literature. Here we report the identification of novel compound heterozygous missense mutations in two affected siblings from a Lebanese family by whole‐exome sequencing. The mutations alter a conserved C‐terminal domain of the encoded protein and reduce protein stability as determined through Western blot analysis of patient fibroblasts. Patient fibroblasts exhibit a lipid droplet phenotype similar to that recently reported in Warburg Micro syndrome, a disorder with similar features but hitherto unrelated cellular etiology. |
| format | Article |
| id | doaj-art-ebe39d83cd9e4ac9b1cc74a82d2be71d |
| institution | Directory of Open Access Journals |
| issn | 2324-9269 |
| language | English |
| publishDate | 2014-07-01 |
| publisher | Wiley |
| record_format | Article |
| spelling | doaj-art-ebe39d83cd9e4ac9b1cc74a82d2be71d2025-08-20T01:55:12ZengWileyMolecular Genetics & Genomic Medicine2324-92692014-07-012431932510.1002/mgg3.70Loss of ALDH18A1 function is associated with a cellular lipid droplet phenotype suggesting a link between autosomal recessive cutis laxa type 3A and Warburg Micro syndromeMark T. Handley0André Mégarbané1Alison M. Meynert2Stephen Brown3Elisabeth Freyer4Martin S. Taylor5Ian J. Jackson6Irene A. Aligianis7MRC Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh UKInstitut Médical Jérôme Lejeune et Fondation Jérome Lejeune Paris FranceMRC Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh UKMRC Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh UKMRC Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh UKMRC Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh UKMRC Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh UKMRC Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh UKAbstract Autosomal recessive cutis laxa type 3A is caused by mutations in ALDH18A1, a gene encoding the mitochondrial enzyme ∆1‐pyrroline‐5‐carboxylate synthase (P5CS). It is a rare disorder with only six pathogenic mutations and 10 affected individuals from five families previously described in the literature. Here we report the identification of novel compound heterozygous missense mutations in two affected siblings from a Lebanese family by whole‐exome sequencing. The mutations alter a conserved C‐terminal domain of the encoded protein and reduce protein stability as determined through Western blot analysis of patient fibroblasts. Patient fibroblasts exhibit a lipid droplet phenotype similar to that recently reported in Warburg Micro syndrome, a disorder with similar features but hitherto unrelated cellular etiology.https://doi.org/10.1002/mgg3.70ARCL3Acutis laxalipid dropletsWarburg Micro syndrome |
| spellingShingle | Mark T. Handley André Mégarbané Alison M. Meynert Stephen Brown Elisabeth Freyer Martin S. Taylor Ian J. Jackson Irene A. Aligianis Loss of ALDH18A1 function is associated with a cellular lipid droplet phenotype suggesting a link between autosomal recessive cutis laxa type 3A and Warburg Micro syndrome ARCL3A cutis laxa lipid droplets Warburg Micro syndrome |
| title | Loss of ALDH18A1 function is associated with a cellular lipid droplet phenotype suggesting a link between autosomal recessive cutis laxa type 3A and Warburg Micro syndrome |
| title_full | Loss of ALDH18A1 function is associated with a cellular lipid droplet phenotype suggesting a link between autosomal recessive cutis laxa type 3A and Warburg Micro syndrome |
| title_fullStr | Loss of ALDH18A1 function is associated with a cellular lipid droplet phenotype suggesting a link between autosomal recessive cutis laxa type 3A and Warburg Micro syndrome |
| title_full_unstemmed | Loss of ALDH18A1 function is associated with a cellular lipid droplet phenotype suggesting a link between autosomal recessive cutis laxa type 3A and Warburg Micro syndrome |
| title_short | Loss of ALDH18A1 function is associated with a cellular lipid droplet phenotype suggesting a link between autosomal recessive cutis laxa type 3A and Warburg Micro syndrome |
| title_sort | loss of aldh18a1 function is associated with a cellular lipid droplet phenotype suggesting a link between autosomal recessive cutis laxa type 3a and warburg micro syndrome |
| topic | ARCL3A cutis laxa lipid droplets Warburg Micro syndrome |
| url | https://doi.org/10.1002/mgg3.70 |
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