ClinVar

Cone-Rod Dystrophy 16

In 2 brothers with cone-rod dystrophy (CORD16; 614500) from a consanguineous family, Estrada-Cuzcano et al. (2012) identified homozygosity for a 529C-T transition in exon 6 of the C8ORF37 gene, resulting in an arg177-to-trp (R177W) substitution at a highly conserved residue. The mutation segregated with disease in the family and was not found in 179 ethnically matched controls or in the 1000 Genomes Project database. The brothers had central isolated macular atrophy and attenuation of retinal vessels; 1 brother also had peripapillar atrophy, temporal optic disc pallor, and pigment clumping, whereas the other did not. Both had nonrecordable cone patterns and severely reduced rod recordings on electroretinography, and visual acuity was reduced to 20/400 in 1 eye for both, whereas visual acuity was 20/250 and 20/60 in the other eye, respectively.

Bardet-Biedl Syndrome 21

In a 6-year-old Saudi Arabian boy with Bardet-Biedl syndrome (BBS21; 617406), Khan et al. (2016) identified homozygosity for the R177W mutation in the C8ORF37 gene. His unaffected consanguineous parents were heterozygous for the mutation. The authors noted that the proband exhibited cone-rod dystrophy rather than the rod-cone dystrophy more commonly seen in BBS. Khan et al. (2016) stated that although modifiers may play a role in variable expressivity, they found no evidence for any pathogenic mutation other than in C8ORF37 that contributed to the disease phenotype in this patient.

Heon et al. (2016) overexpressed R177W C8orf37 in zebrafish embryos and evaluated them for BBS-related phenotypes. They observed statistically significant Kupffer vesicle formation defects, melanosome transport delays, and visual impairment. In addition, the R177W mutant failed to significantly rescue morpholino-induced zebrafish knockdown phenotypes.