A novel C8orf37 splice mutation and genotype-phenotype correlation for cone-rod dystrophy

ABSTRACT

Background: To identify the disease-causing mutation in a consanguineous family of Morrocan origin with syndromic autosomal recessive (ar) cone-rod dystrophy (CRD) in two patients and describe genotype-phenotype correlations.

Materials and Methods: Genome-wide homozygosity mapping and direct sequencing of C8orf37, located in a homozygous interval, was performed in the family. mRNA analysis revealed the effect of the newly identified splice-site mutation. For a comparative analysis phenotypic and genetic data of C8orf37 mutations were extracted from published cases.

Results: The new splice-site mutation c.155+2T>C identified in the family results in a skipping of 82 bp. The CRD phenotypes of our patients were consistent with previous reports. Non-ocular findings in our patients and two previously described patients were postaxial polydactyly present at birth. Both families with additional postaxial polydactyly had splice site mutations affecting intron 1 of C8orf37, one at the slice donor and one at the splice acceptor site.

Conclusions: This report extends the genotypic spectrum of C8orf37-associated retinal dystrophies and demonstrates for the first time a genotype-phenotype correlation between an arCRD-polydactyly-association and truncating germline mutations affecting the N-terminal region of the protein. Furthermore, our findings underline the ciliary function of C8orf37 protein.

KEYWORDS:

• Ciliopathy
• cone-rod dystrophy
• C8orf37
• genotype-phenotype correlation
• postaxial polydactyly

Acknowledgments

The authors thank all patients and their attending doctors for their participation in this study. We thank Markus Nussbaum for his reliable 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

The work was supported by funds from the Institute of Human Genetics, Heinrich-Heine University, Düsseldorf, Germany.

Additional information

Funding

The work was supported by funds from the Institute of Human Genetics, Heinrich-Heine University, Düsseldorf, Germany.