Mutations in C8orf37, encoding a ciliary protein, are associated with autosomal-recessive retinal dystrophies with early macular involvement.

Cuzcano Alejandro Estrada

Researchers of the Departments of Human Genetics and Ophthalmology have identified a novel gene that is mutated in individuals with autosomal recessive retinitis pigmentosa (RP) or cone-rod dystrophy (CRD). The mutated gene (C8orf37) was identified using a combination of homozygosity mapping and next-generation sequencing. C8orf37 encodes a protein that is located at the base of the connecting cilium of photoreceptor cells. These results were published on 13 January 2012 in the American Journal of Human Genetics.


Genome-wide homozygosity mapping in one individual with RP in a consanguineous German family resulted in the identification of three outstanding homozygous regions. Targeted NGS revealed a homozygous stopmutation in C8orf37, located in the largest homozygous region on chromosome 8. To quickly search for additional families with mutations in this gene, the Nijmegen group made use of homozygosity mapping data in retinal dystrophy families from 9 collaborating groups that are part of the European Retinal Disease Consortium (ERDC). ERDC members collectively ascertained 6.000 families with inherited retinal dystrophies and performed homozygosity mapping in patients of 600 families.
In 7 individuals with retinal dystrophy of three additional consanguineous families from Israel and the Netherlands, mutations were found in the C8orf37 gene, thereby providing further proof of the involvement of this gene in progressive retinal dystrophies. Future studies will investigate its exact role in the connecting cilium and its mutational load in patients with RP or CRD.


Estrada-Cuzcano, A., Neveling, K., Kohl, S., Banin, E., Rotenstreich, Y., Sharon, D., Falik-Zaccai, T. C., Hipp, S., Roepman, R., Wissinger, B., Letteboer, S. J. F., Mans, D. A., Blokland, E., Kwint, M. P.,  Gijsen, S. J., van Huet, R. A. C., Collin, R. W. J., Scheffer, H., Veltman, J.A., Zrenner, E., the European Retinal Disease Consortium, den Hollander, A. I., Klevering, B. J. & Cremers, F. P. M. Mutations in C8orf37, encoding a ciliary protein, are associated with autosomal-recessive retinal dystrophies with early macular involvement. Am. J. Hum. Genet. 90, 202-109, 2012.


<< back to overview news items