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Abstract
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.
- cornea
- dystrophy
- genetics
Data availability statement
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.
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Footnotes
Contributors ZC performed experimentation, mutation screening of SLC4A11 in patients, and unaffected members of the two studied families using Sanger sequencing. She also wrote the molecular part of the manuscript. IZA identified patients and recruited all family members. She provided from them blood samples and detailed clinical data and also wrote the clinical part of the manuscript. JF supervised clinical examination and facilitated ophthalmologic explorations performed on CHED patients. PS provided products and equipment for experimentation. MHA was responsible for conception and design of the study and supervised together with PS the work as a part of a mutual Tuniso-swidish project on Eye disease.
Funding This study was funded by Ministry of Higher Education and Scientific Research-Tunisia. (LR16E16) and by Foundation of Synfrämjandets Forskningsfond/Ögonfonden (www.ögonfonden.se).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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