Molecular genetic characterization of Congolese patients with oculocutaneous albinism

Background: Oculocutaneous albinism (OCA) is an autosomal recessive genetic disorder associated with reduced or absent pigmentation in the skin, hair and eyes. OCA type 2 (OCA2) is the most common type in Sub-Saharan Africa, related to a recurrent 2.7 kb intragenic deletion. Genomic data from Congolese patients are lacking. We aimed to describe genetic causes of OCA2 in a cohort of Congolese persons with OCA, and explore possible genotype-phenotype correlations.Methods: A cross sectional study was conducted from January 2015 to December 2017 in Kinshasa, Democratic Republic of Congo (DRC). 165 Congolese unrelated families with non-syndromic OCA, identified through pa-tients' associations, consented to participate to this study. All index cases were tested for the known 2.7 kb deletion involving the exon 7 of the OCA2 gene. Patients heterozygous for the deletion underwent Sanger sequencing of all exons and flanking sequences in the OCA2 gene. Family segregation was performed for candidate pathogenic variants.Results: The 2.7 kb deletion in the OCA2 gene was identified in 136/165 (82.4%) index cases, including 113 (68.5%) homozygotes and 23 (13.9%) heterozygotes. Sanger sequencing identified a pathogenic or likely pathogenic variant in the OCA2 gene in 12 out of 23 heterozygotes investigated (52.1%). Segregation analysis allowed us to locate the point mutation on the trans allele in the three patients from whom parental DNA was available.Conclusion: The OCA2 2.7 kb deletion is the major cause of non-syndromic OCA in Congolese patients recruited in this study, confirming results from other Sub-Saharan African populations. Several additional mutations were detected in OCA patient's heterozygote for the deletion, with to date no evidence for a second frequent founder mutation. The confirmation of a single mutation as the major cause will facilitate genetic counselling in this country.

Automated summary

This study found that the 2.7kb deletion in the OCA2 gene is the major cause of OCA in Congolese patients, with additional mutations detected in heterozygotes but no evidence of a second frequent founder mutation. This confirmation of a single mutation as the major cause will facilitate genetic counselling in the country.