Mutational Analysis of the SLC4A11 Gene in a (Filipino) Family with Congenital Hereditary Endothelial Dystrophy

Abstract

Aim: The study aims to identify if mutations in the SLC4A11 gene are present in Filipino families affected with congenital hereditary endothelial dystrophy (CHED). Methods: This is a family cohort study that investigated the genetic profile of a selected family in northern Luzon, Philippines, whose members were diagnosed with congenital hereditary endothelial dystrophy (CHED). A patient who was diagnosed with CHED prior to this study served as the proband for this family. A detailed family history was obtained and a complete ophthalmologic examination was performed on each of the family members. A total of six affected members and three unaffected members were included in this study. DNA was isolated from peripheral blood samples of the family members, polymerase chain reaction (PCR) was used to amplify the gene’s entire coding region (19 exons and 2 putative promoter regions), and finally, the amplified regions were analyzed using DNA sequencing. Results: Consanguinity was not present in the family. Corneal haze was reported to have been present since birth or shortly thereafter in all the affected patients. Slit-lamp examination showed edematous corneas. Molecular studies of the SLC4A11 gene revealed four novel homozygous point mutations variably presenting in the six affected members, as well as the three unaffected members. One unaffected family member (I-1) had a novel sense mutation absent in the other family members. All affected siblings showed little phenotypic variability. Conclusions: This is the first report that gives us a genetic profile of a northern Luzon family with members affected by CHED. This study supports earlier findings that mutations in the SLC4A11 gene are not consistently the same among different ethnic groups worldwide, probably due to the disease’s genetic heterogeneity. Our study documented five novel mutations, adding to the growing list of mutations probably responsible for acquiring the CHED phenotype. It is possible that there are more novel mutations waiting to be discovered in this hereditary disease. Screening for these specific mutations in other families may prove useful for genetic counseling, prenatal diagnosis, and the future development of gene therapy.