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Correction published on 23 October 2017, see Genes 2017, 8(10), 286.

Open AccessArticle
Genes 2017, 8(9), 210; doi:10.3390/genes8090210

Whole Genome Sequencing Revealed Mutations in Two Independent Genes as the Underlying Cause of Retinal Degeneration in an Ashkenazi Jewish Pedigree

1
Ophthalmology, University of California, San Francisco, San Francisco, CA 94143-0730, USA
2
REVA University, Bengaluru, Karnataka 560034, India
3
Shiley Eye Institute, University of California, San Diego, La Jolla, CA 92093-0946, USA
4
Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA
5
Human Longevity, Inc., San Diego, CA 92121, USA
6
Department of Pediatrics, Rady Children’s Hospital, Division of Genome Information Sciences, San Diego, CA 92093, USA
*
Author to whom correspondence should be addressed.
Received: 30 June 2017 / Revised: 5 August 2017 / Accepted: 18 August 2017 / Published: 24 August 2017
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Abstract

Retinitis pigmentosa (RP) causes progressive photoreceptor loss resulting from mutations in over 80 genes. This study identified the genetic cause of RP in three members of a non-consanguineous pedigree. Detailed ophthalmic evaluation was performed in the three affected family members. Whole exome sequencing (WES) and whole genome sequencing (WGS) were performed in the three affected and the two unaffected family members and variants were filtered to detect rare, potentially deleterious variants segregating with disease. WES and WGS did not identify potentially pathogenic variants shared by all three affected members. However, WES identified a previously reported homozygous nonsense mutation in KIZ (c.226C>T, p.Arg76*) in two affected sisters, but not in their affected second cousin. WGS revealed a novel 1.135 kb homozygous deletion in a retina transcript of C21orf2 and a novel 30.651 kb heterozygous deletion in CACNA2D4 in the affected second cousin. The sisters with the KIZ mutation carried no copies of the C21orf2 or CACNA2D4 deletions, while the second cousin with the C21orf2 and CACNA2D4 deletions carried no copies of the KIZ mutation. This study identified two independent, homozygous mutations in genes previously reported in autosomal recessive RP in a non-consanguineous family, and demonstrated the value of WGS when WES fails to identify likely disease-causing mutations. View Full-Text
Keywords: retina; genetics; retinitis pigmentosa retina; genetics; retinitis pigmentosa
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MDPI and ACS Style

Gustafson, K.; Duncan, J.L.; Biswas, P.; Soto-Hermida, A.; Matsui, H.; Jakubosky, D.; Suk, J.; Telenti, A.; Frazer, K.A.; Ayyagari, R. Whole Genome Sequencing Revealed Mutations in Two Independent Genes as the Underlying Cause of Retinal Degeneration in an Ashkenazi Jewish Pedigree. Genes 2017, 8, 210.

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