PT - JOURNAL ARTICLE AU - Chibani, Zohra AU - Abid, Imen Zone AU - Söderkvist, Peter AU - Feki, Jamel AU - Aifa, Mounira Hmani TI - Autosomal recessive congenital hereditary corneal dystrophy associated with a novel <em>SLC4A11</em> mutation in two consanguineous Tunisian families AID - 10.1136/bjophthalmol-2020-318204 DP - 2022 Feb 01 TA - British Journal of Ophthalmology PG - 281--287 VI - 106 IP - 2 4099 - http://bjo.bmj.com/content/106/2/281.short 4100 - http://bjo.bmj.com/content/106/2/281.full SO - Br J Ophthalmol2022 Feb 01; 106 AB - Background Autosomal recessive congenital hereditary corneal dystrophy (CHED) is a rare isolated developmental anomaly of the eye characterised by diffuse bilateral corneal clouding that may lead to visual impairment requiring corneal transplantation. CHED is known to be caused by mutations in the solute carrier family 4 member 11 (SLC4A11) gene which encodes a membrane transporter protein (sodium bicarbonate transporter-like solute carrier family 4 member 11).Methods To identify SLC4A11 gene mutations associated with CHED (OMIM: #217700), genomic DNA was extracted from whole blood and sequenced for all exons and intron-exon boundaries in two large Tunisian families.Results A novel deletion SLC4A11 mutation (p. Leu479del; c.1434_1436del) is responsible for CHED in both analysed families. This non-frameshift mutation was found in a homozygous state in affected members and heterozygous in non-affected members. In silico analysis largely support the pathogenicity of this alteration that may leads to stromal oedema by disrupting the osmolarity balance. Being localised to a region of alpha-helical secondary structure, Leu479 deletion may induce protein-compromising structural rearrangements.Conclusion To the best of our knowledge, this is the first clinical and genetic study exploring CHED in Tunisia. The present work also expands the list of pathogenic genotypes in SLC4A11 gene and its associated clinical diagnosis giving more insights into genotype–phenotype correlations.Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information table S1.