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A tapt1 knock-out zebrafish line with aberrant lens development and impaired vision models human early-onset cataract

(2023) HUMAN GENETICS. 142(3). p.457-476
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Abstract
Bi-allelic mutations in the gene coding for human trans-membrane anterior–posterior transformation protein 1 (TAPT1) result in a broad phenotypic spectrum, ranging from syndromic disease with severe skeletal and congenital abnormalities to isolated early-onset cataract. We present here the first patient with a frameshift mutation in the TAPT1 gene, resulting in both bilateral early-onset cataract and skeletal abnormalities, in addition to several dysmorphic features, in this way further expanding the phenotypic spectrum associated with TAPT1 mutations. A tapt1a/tapt1b double knock-out (KO) zebrafish model generated by CRISPR/Cas9 gene editing revealed an early larval phenotype with eye malformations, loss of vision, increased photokinetics and hyperpigmentation, without visible skeletal involvement. Ultrastructural analysis of the eyes showed a smaller condensed lens, loss of integrity of the lens capsule with formation of a secondary lens and hyperplasia of the cells in the ganglion and inner plexiform layers of the retina. Transcriptomic analysis pointed to an impaired lens development with aberrant expression of many of the crystallin and other lens-specific genes. Furthermore, the phototransduction and visual perception pathways were found to be significantly disturbed. Differences in light perception are likely the cause of the increased dark photokinetics and generalized hyperpigmentation observed in this zebrafish model. In conclusion, this study validates TAPT1 as a new gene for early-onset cataract and sheds light on its ultrastructural and molecular characteristics.
Keywords
Genetics (clinical), Genetics, Rare disorders, Zebrafish, IN-VIVO, DISRUPTION, PHENOTYPES, TRANSPORT, GENETICS, RECEPTOR, PROTECTS, GENOMICS, MUTATION, REVEALS

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Citation

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MLA
Jarayseh, Tamara, et al. “A Tapt1 Knock-out Zebrafish Line with Aberrant Lens Development and Impaired Vision Models Human Early-Onset Cataract.” HUMAN GENETICS, vol. 142, no. 3, 2023, pp. 457–76, doi:10.1007/s00439-022-02518-w.
APA
Jarayseh, T., Guillemyn, B., De Saffel, H., Bek, J. W., Syx, D., Symoens, S., … Willaert, A. (2023). A tapt1 knock-out zebrafish line with aberrant lens development and impaired vision models human early-onset cataract. HUMAN GENETICS, 142(3), 457–476. https://doi.org/10.1007/s00439-022-02518-w
Chicago author-date
Jarayseh, Tamara, Brecht Guillemyn, Hanna De Saffel, Jan Willem Bek, Delfien Syx, Sofie Symoens, Yannick Gansemans, et al. 2023. “A Tapt1 Knock-out Zebrafish Line with Aberrant Lens Development and Impaired Vision Models Human Early-Onset Cataract.” HUMAN GENETICS 142 (3): 457–76. https://doi.org/10.1007/s00439-022-02518-w.
Chicago author-date (all authors)
Jarayseh, Tamara, Brecht Guillemyn, Hanna De Saffel, Jan Willem Bek, Delfien Syx, Sofie Symoens, Yannick Gansemans, Filip Van Nieuwerburgh, Sujatha Jagadeesh, Jayarekha Raja, Fransiska Malfait, Paul Coucke, Adelbert De Clercq, and Andy Willaert. 2023. “A Tapt1 Knock-out Zebrafish Line with Aberrant Lens Development and Impaired Vision Models Human Early-Onset Cataract.” HUMAN GENETICS 142 (3): 457–476. doi:10.1007/s00439-022-02518-w.
Vancouver
1.
Jarayseh T, Guillemyn B, De Saffel H, Bek JW, Syx D, Symoens S, et al. A tapt1 knock-out zebrafish line with aberrant lens development and impaired vision models human early-onset cataract. HUMAN GENETICS. 2023;142(3):457–76.
IEEE
[1]
T. Jarayseh et al., “A tapt1 knock-out zebrafish line with aberrant lens development and impaired vision models human early-onset cataract,” HUMAN GENETICS, vol. 142, no. 3, pp. 457–476, 2023.
@article{01GSA7CPJKHRZ90Y2XQD96TY6D,
  abstract     = {{Bi-allelic mutations in the gene coding for human trans-membrane anterior–posterior transformation protein 1 (TAPT1) result in a broad phenotypic spectrum, ranging from syndromic disease with severe skeletal and congenital abnormalities to isolated early-onset cataract. We present here the first patient with a frameshift mutation in the TAPT1 gene, resulting in both bilateral early-onset cataract and skeletal abnormalities, in addition to several dysmorphic features, in this way further expanding the phenotypic spectrum associated with TAPT1 mutations. A tapt1a/tapt1b double knock-out (KO) zebrafish model generated by CRISPR/Cas9 gene editing revealed an early larval phenotype with eye malformations, loss of vision, increased photokinetics and hyperpigmentation, without visible skeletal involvement. Ultrastructural analysis of the eyes showed a smaller condensed lens, loss of integrity of the lens capsule with formation of a secondary lens and hyperplasia of the cells in the ganglion and inner plexiform layers of the retina. Transcriptomic analysis pointed to an impaired lens development with aberrant expression of many of the crystallin and other lens-specific genes. Furthermore, the phototransduction and visual perception pathways were found to be significantly disturbed. Differences in light perception are likely the cause of the increased dark photokinetics and generalized hyperpigmentation observed in this zebrafish model. In conclusion, this study validates TAPT1 as a new gene for early-onset cataract and sheds light on its ultrastructural and molecular characteristics.}},
  author       = {{Jarayseh, Tamara and Guillemyn, Brecht and De Saffel, Hanna and Bek, Jan Willem and Syx, Delfien and Symoens, Sofie and Gansemans, Yannick and Van Nieuwerburgh, Filip and Jagadeesh, Sujatha and Raja, Jayarekha and Malfait, Fransiska and Coucke, Paul and De Clercq, Adelbert and Willaert, Andy}},
  issn         = {{0340-6717}},
  journal      = {{HUMAN GENETICS}},
  keywords     = {{Genetics (clinical),Genetics,Rare disorders,Zebrafish,IN-VIVO,DISRUPTION,PHENOTYPES,TRANSPORT,GENETICS,RECEPTOR,PROTECTS,GENOMICS,MUTATION,REVEALS}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{457--476}},
  title        = {{A tapt1 knock-out zebrafish line with aberrant lens development and impaired vision models human early-onset cataract}},
  url          = {{http://doi.org/10.1007/s00439-022-02518-w}},
  volume       = {{142}},
  year         = {{2023}},
}

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