PT  - JOURNAL ARTICLE
AU  - Nicole Weisschuh
AU  - Britta Feldhaus
AU  - Muhammad Imran Khan
AU  - Frans P. M. Cremers
AU  - Susanne Kohl
AU  - Bernd Wissinger
AU  - Ditta Zobor
TI  - Molecular and clinical analysis of 27 German patients with Leber congenital amaurosis
AID  - 10.1101/428177
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 428177
4099  - http://biorxiv.org/content/early/2018/09/26/428177.short
4100  - http://biorxiv.org/content/early/2018/09/26/428177.full
AB  - 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.