Molecular and clinical analysis of 27 German patients with Leber congenital amaurosis.
Leber congenital amaurosis (LCA) is the earliest and most severe form of all inherited retinal dystrophies (IRD) and the most frequent cause of inherited blindness in children. The phenotypic overlap with other early-onset and severe IRDs as well as difficulties associated with the ophthalmic examin...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0205380 |
| _version_ | 1819114022257033216 |
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| author | Nicole Weisschuh Britta Feldhaus Muhammad Imran Khan Frans P M Cremers Susanne Kohl Bernd Wissinger Ditta Zobor |
| author_facet | Nicole Weisschuh Britta Feldhaus Muhammad Imran Khan Frans P M Cremers Susanne Kohl Bernd Wissinger Ditta Zobor |
| author_sort | Nicole Weisschuh |
| collection | DOAJ |
| description | Leber congenital amaurosis (LCA) is the earliest and most severe form of all inherited retinal dystrophies (IRD) and the most frequent cause of inherited blindness in children. The phenotypic overlap with other early-onset and severe IRDs as well as difficulties associated with the ophthalmic examination of infants can complicate the clinical diagnosis. To date, 25 genes have been implicated in the pathogenesis of LCA. The disorder is usually inherited in an autosomal recessive fashion, although rare dominant cases have been reported. We report the mutation spectra and frequency of genes in 27 German index patients initially diagnosed with LCA. A total of 108 LCA- and other genes implicated in IRD were analysed using a cost-effective targeted next-generation sequencing procedure based on molecular inversion probes (MIPs). Sequencing and variant filtering led to the identification of putative pathogenic variants in 25 cases, thereby leading to a detection rate of 93%. The mutation spectrum comprises 34 different alleles, 17 of which are novel. In line with previous studies, the genetic results led to a revision of the initial clinical diagnosis in a substantial proportion of cases, demonstrating the importance of genetic testing in IRD. In addition, our detection rate of 93% shows that MIPs are a cost-efficient and sensitive tool for targeted next-generation sequencing in IRD. |
| first_indexed | 2024-12-22T04:38:41Z |
| format | Article |
| id | doaj.art-f69a5c50f2054cd6bfd8738d04999f48 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T04:38:41Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f69a5c50f2054cd6bfd8738d04999f482022-12-21T18:38:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-011312e020538010.1371/journal.pone.0205380Molecular and clinical analysis of 27 German patients with Leber congenital amaurosis.Nicole WeisschuhBritta FeldhausMuhammad Imran KhanFrans P M CremersSusanne KohlBernd WissingerDitta ZoborLeber congenital amaurosis (LCA) is the earliest and most severe form of all inherited retinal dystrophies (IRD) and the most frequent cause of inherited blindness in children. The phenotypic overlap with other early-onset and severe IRDs as well as difficulties associated with the ophthalmic examination of infants can complicate the clinical diagnosis. To date, 25 genes have been implicated in the pathogenesis of LCA. The disorder is usually inherited in an autosomal recessive fashion, although rare dominant cases have been reported. We report the mutation spectra and frequency of genes in 27 German index patients initially diagnosed with LCA. A total of 108 LCA- and other genes implicated in IRD were analysed using a cost-effective targeted next-generation sequencing procedure based on molecular inversion probes (MIPs). Sequencing and variant filtering led to the identification of putative pathogenic variants in 25 cases, thereby leading to a detection rate of 93%. The mutation spectrum comprises 34 different alleles, 17 of which are novel. In line with previous studies, the genetic results led to a revision of the initial clinical diagnosis in a substantial proportion of cases, demonstrating the importance of genetic testing in IRD. In addition, our detection rate of 93% shows that MIPs are a cost-efficient and sensitive tool for targeted next-generation sequencing in IRD.https://doi.org/10.1371/journal.pone.0205380 |
| spellingShingle | Nicole Weisschuh Britta Feldhaus Muhammad Imran Khan Frans P M Cremers Susanne Kohl Bernd Wissinger Ditta Zobor Molecular and clinical analysis of 27 German patients with Leber congenital amaurosis. PLoS ONE |
| title | Molecular and clinical analysis of 27 German patients with Leber congenital amaurosis. |
| title_full | Molecular and clinical analysis of 27 German patients with Leber congenital amaurosis. |
| title_fullStr | Molecular and clinical analysis of 27 German patients with Leber congenital amaurosis. |
| title_full_unstemmed | Molecular and clinical analysis of 27 German patients with Leber congenital amaurosis. |
| title_short | Molecular and clinical analysis of 27 German patients with Leber congenital amaurosis. |
| title_sort | molecular and clinical analysis of 27 german patients with leber congenital amaurosis |
| url | https://doi.org/10.1371/journal.pone.0205380 |
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