First Insights Into the Phenotype and Genotype of Inherited Retinal Disorders in the Democratic Republic of Congo (DRC).

Abstract

Purpose/introduction: Inherited retinal disorders (IRD) are a highly heterogeneous group of retinal diseases often characterized by progressive bilateral degeneration of rod and cone photoreceptors. Very little information is available on the genotype and phenotype of IRD in Central Africa. We investigated genetic causes of IRD in a well-characterized group of patients from the Democratic Republic of Congo (DRC).

Materials and methods: Ten patients, from eight families, with a clinical diagnosis of IRD in Kinshasa (DRC) were investigated. Each patient underwent general, dysmorphological and ophthalmic examination. DNA was extracted in the Centre for Human Genetics of the University of Kinshasa and clinical Whole Genome Sequencing (cWGS) was performed at Illumina Clinical Service Laboratory through the Illumina iHope program.

Results: The eight probands comprised 4 males and 4 females aged between 17.5 and 76 years. Nyctalopia and reduced visual acuity were the main complaints. All patients had normal hearing and were nondysmorphic. Fundus examination revealed bone-spicule pigment in all patients. Twelve plausible causal variants were identified in six genes: ADAM9, RP1, MERTK, CYP4V2, USH2A, and IFT140. One SNV and one intragenic CNV were novel. The SNV was assumed to be in trans with an intragenic SNV in three families, consistent with the well-known autosomal recessive inheritance for IRD in those genes.

Conclusion: We report on the first cohort of African IRD patients investigated by cWGS. Our results indicate that also in Congolese patients, the spectrum of causal genes is broad and we expand the spectrum of causal variants in known IRD genes. This report demonstrates the power of cWGS, especially for genetically heterogeneous diseases.