On variants and disease-causing mutations: Case studies of a SEMA4A variant identified in inherited blindness

ABSTRACT

The p.R713Q variant of the semaphorin‐4a‐encoding gene, SEMA4a, has been reported to cause autosomal dominant retinitis pigmentosa. Here we show three families with retinal degeneration in which unaffected family members are either homozygous or heterozygous for the variant. The p.R713Q variant in SEMA4A is insufficient to cause either autosomal recessive or autosomal dominant retinitis pigmentosa and is unlikely to be pathogenic.

KEYWORDS:

• SEMA4A
• retinitis pigmentosa
• macular degeneration
• genetic diagnosis
• variant analysis
• next generation sequencing

Acknowledgments

We thank the participants and their families for participating in this study and Jeannette Bennicelli for technical assistance.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Funding

This work was supported by the Pennsylvania Department of Health, Foundation Fighting Blindness-sponsored CHOP-Penn Pediatric Center for Retinal Degenerations, National Eye Institute/NIH grant R24EY019861, NIH Vision Training Grant 5T32EY007035-37, Research to Prevent Blindness, the Paul and Evanina Mackall Foundation Trust, the Scheie Eye Institute, the Center for Advanced Retinal and Ocular Therapeutics, the F.M. Kirby Foundation.

Additional information

Funding

This work was supported by the Pennsylvania Department of Health, Foundation Fighting Blindness-sponsored CHOP-Penn Pediatric Center for Retinal Degenerations, National Eye Institute/NIH grant R24EY019861, NIH Vision Training Grant 5T32EY007035-37, Research to Prevent Blindness, the Paul and Evanina Mackall Foundation Trust, the Scheie Eye Institute, the Center for Advanced Retinal and Ocular Therapeutics, the F.M. Kirby Foundation.