Background/aims SLC4A11 is the only known causative gene of congenital hereditary endothelial dystrophy (CHED). Mutation screenings have shown that most but not all patients with CHED harbour mutations in SLC4A11, suggesting that other CHED-causing genes may exist. We aimed to screen SLC4A11 in Iranian patients to learn the mutation spectrum of this gene among Iranians and to gain further knowledge on potential contribution of other genes to CHED aetiology.
Methods SLC4A11 was screened in 21 Iranian patients with CHED by sequencing. Previously unreported variations were checked in at least 200 controls, and segregation analysis within families and bioinformatics predictions on effects of variations were performed. Exome sequencing was done for the single patient without an SLC4A11 mutation and for her parents.
Results Nine previously reported and 10 unreported SLC4A11 mutations were observed among 20 patients; a mutation was not found in one patient. A mutation in MPDZ was identified as the only candidate cause of CHED in this patient. Her mother who carried the same mutation was diagnosed with Fuchs endothelial corneal dystrophy (FECD).
Conclusion SLC4A11 mutations are the usual cause of CHED in Iranians. The 10 novel mutations observed contribute significantly to the approximately 85 mutations reported since discovery of the role of the gene in CHED pathogenesis more than 10 years ago. MPDZ mutations may be a cause of CHED and even FECD in a minority of patients. Proposed functions of MPDZ with respect to tight junctions and maintenance of the corneal endothelial barrier are in accordance with a role in corneal endothelial pathobiology.
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Contributors HM recruited patients and family members, was involved in analysis of exome data, performed mutation screening of SLC4A11 in patients and segregation analysis in their families by Sanger sequencing, and contributed to writing of the manuscript. MAJ, MRPB, MHT, FK and BH identified patients and provided clinical data. DA, MK, ME and AM performed mutation screening of SLC4A11 in patients and segregation analysis in their families by Sanger sequencing. TNM and HH contributed to patient and control recruitment and obtaining blood from these individuals. MTA provided materials and consultation. EE designed and supervised the research, and wrote the manuscript.
Funding This study was supported by the National Institute for Medical Research Development (NIMAD) and the Ophthalmic Research Center of Shahid Beheshti University of Medical Sciences. HM was supported by postdoctoral fellowship from Iran National Science Foundation (No 96012574).
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval Ethics board of the Ophthalmic Research Center of Shahid Beheshti University of Medical Sciences (ID: IR.SBMU.UNRC1395.8).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.