Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis
Background Corneal intraepithelial dyskeratosis is an extremely rare condition. The classical form, affecting Native American Haliwa-Saponi tribe members, is called hereditary benign intraepithelial dyskeratosis (HBID). Herein, we present a new form of corneal intraepithelial dyskeratosis for which...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2013
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| Online Access: | https://hdl.handle.net/10356/105013 http://hdl.handle.net/10220/16570 |
| _version_ | 1826127016672362496 |
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| author | Maurer-Stroh, Sebastian Soler, V. J. Tran-Viet, K.-N. Galiacy, S. D. Limviphuvadh, V. Klemm, T. P. St Germain, E. Fournie, P. R. Guillaud, C. Hawthorne, F. Suarez, C. Kantelip, B. Afshari, N. A. Creveaux, I. Luo, X. Meng, W. Calvas, P. Cassagne, M. Arne, J.-L. Malecaze, F. Young, T. L. Rozen, Steve G. |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Maurer-Stroh, Sebastian Soler, V. J. Tran-Viet, K.-N. Galiacy, S. D. Limviphuvadh, V. Klemm, T. P. St Germain, E. Fournie, P. R. Guillaud, C. Hawthorne, F. Suarez, C. Kantelip, B. Afshari, N. A. Creveaux, I. Luo, X. Meng, W. Calvas, P. Cassagne, M. Arne, J.-L. Malecaze, F. Young, T. L. Rozen, Steve G. |
| author_sort | Maurer-Stroh, Sebastian |
| collection | NTU |
| description | Background Corneal intraepithelial dyskeratosis is an extremely rare condition. The classical form, affecting Native American Haliwa-Saponi tribe members, is called hereditary benign intraepithelial dyskeratosis (HBID). Herein, we present a new form of corneal intraepithelial dyskeratosis for which we identified the causative gene by using deep sequencing technology.
Methods and results A seven member Caucasian French family with two corneal intraepithelial dyskeratosis affected individuals (6-year-old proband and his mother) was ascertained. The proband presented with bilateral complete corneal opacification and dyskeratosis. Palmoplantar hyperkeratosis and laryngeal dyskeratosis were associated with the phenotype. Histopathology studies of cornea and vocal cord biopsies showed dyskeratotic keratinisation. Quantitative PCR ruled out 4q35 duplication, classically described in HBID cases. Next generation sequencing with mean coverage of 50× using the Illumina Hi Seq and whole exome capture processing was performed. Sequence reads were aligned, and screened for single nucleotide variants and insertion/deletion calls. In-house pipeline filtering analyses and comparisons with available databases were performed. A novel missense mutation M77T was discovered for the gene NLRP1 which maps to chromosome 17p13.2. This was a de novo mutation in the proband's mother, following segregation in the family, and not found in 738 control DNA samples. NLRP1 expression was determined in adult corneal epithelium. The amino acid change was found to destabilise significantly the protein structure.
Conclusions We describe a new corneal intraepithelial dyskeratosis and how we identified its causative gene. The NLRP1 gene product is implicated in inflammation, autoimmune disorders, and caspase mediated apoptosis. NLRP1 polymorphisms are associated with various diseases. |
| first_indexed | 2024-10-01T07:01:52Z |
| format | Journal Article |
| id | ntu-10356/105013 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:01:52Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | ntu-10356/1050132022-02-16T16:30:36Z Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis Maurer-Stroh, Sebastian Soler, V. J. Tran-Viet, K.-N. Galiacy, S. D. Limviphuvadh, V. Klemm, T. P. St Germain, E. Fournie, P. R. Guillaud, C. Hawthorne, F. Suarez, C. Kantelip, B. Afshari, N. A. Creveaux, I. Luo, X. Meng, W. Calvas, P. Cassagne, M. Arne, J.-L. Malecaze, F. Young, T. L. Rozen, Steve G. School of Biological Sciences Bioinformatics Research Centre DRNTU::Science::Biological sciences Background Corneal intraepithelial dyskeratosis is an extremely rare condition. The classical form, affecting Native American Haliwa-Saponi tribe members, is called hereditary benign intraepithelial dyskeratosis (HBID). Herein, we present a new form of corneal intraepithelial dyskeratosis for which we identified the causative gene by using deep sequencing technology. Methods and results A seven member Caucasian French family with two corneal intraepithelial dyskeratosis affected individuals (6-year-old proband and his mother) was ascertained. The proband presented with bilateral complete corneal opacification and dyskeratosis. Palmoplantar hyperkeratosis and laryngeal dyskeratosis were associated with the phenotype. Histopathology studies of cornea and vocal cord biopsies showed dyskeratotic keratinisation. Quantitative PCR ruled out 4q35 duplication, classically described in HBID cases. Next generation sequencing with mean coverage of 50× using the Illumina Hi Seq and whole exome capture processing was performed. Sequence reads were aligned, and screened for single nucleotide variants and insertion/deletion calls. In-house pipeline filtering analyses and comparisons with available databases were performed. A novel missense mutation M77T was discovered for the gene NLRP1 which maps to chromosome 17p13.2. This was a de novo mutation in the proband's mother, following segregation in the family, and not found in 738 control DNA samples. NLRP1 expression was determined in adult corneal epithelium. The amino acid change was found to destabilise significantly the protein structure. Conclusions We describe a new corneal intraepithelial dyskeratosis and how we identified its causative gene. The NLRP1 gene product is implicated in inflammation, autoimmune disorders, and caspase mediated apoptosis. NLRP1 polymorphisms are associated with various diseases. 2013-10-18T02:14:44Z 2019-12-06T21:44:30Z 2013-10-18T02:14:44Z 2019-12-06T21:44:30Z 2013 2013 Journal Article Soler, V. J., Tran-Viet, K. N., Galiacy, S. D., Limviphuvadh, V., Klemm, T. P., St Germain, E., Fournie, P. R., Guillaud, C., Maurer-Stroh, S., Hawthorne, F., Suarez, C., Kantelip, B., Afshari, N. A., Creveaux, I., Luo, X., Meng, W., Calvas, P., Cassagne, M., Arne, J. L., Rozen, S. G., Malecaze, F.,& Young, T. L. (2013). Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis. Journal of Medical Genetics, 50(4), 246-254. https://hdl.handle.net/10356/105013 http://hdl.handle.net/10220/16570 10.1136/jmedgenet-2012-101325 23349227 en Journal of medical genetics |
| spellingShingle | DRNTU::Science::Biological sciences Maurer-Stroh, Sebastian Soler, V. J. Tran-Viet, K.-N. Galiacy, S. D. Limviphuvadh, V. Klemm, T. P. St Germain, E. Fournie, P. R. Guillaud, C. Hawthorne, F. Suarez, C. Kantelip, B. Afshari, N. A. Creveaux, I. Luo, X. Meng, W. Calvas, P. Cassagne, M. Arne, J.-L. Malecaze, F. Young, T. L. Rozen, Steve G. Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis |
| title | Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis |
| title_full | Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis |
| title_fullStr | Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis |
| title_full_unstemmed | Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis |
| title_short | Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis |
| title_sort | whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis |
| topic | DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/105013 http://hdl.handle.net/10220/16570 |
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