Elongated axial length and myopia-related fundus changes associated with the Arg130Cys mutation in the gene in four Chinese families with congenital cataracts.

BACKGROUND

Congenital cataract (CC) is a congenital abnormality characterized by lens opacity present at birth and is associated with highly heterogeneous clinical manifestations. Lens-specific integral membrane protein () gene expression is localized to tight junctional domains of different lens fiber membranes. To date, only four mutations in have been reported to be associated with congenital or presenile cataracts. Due to the rarity of variants detected in the gene, there is limited progress in understanding the correlation between the genotype and phenotype of patients with mutations in .

METHODS

A total of four Chinese families with CCs were recruited for this study, including three families inheriting in an autosomal dominant (AD) pattern and one sporadic case. Genomic DNA was extracted from the leukocytes of peripheral blood collected from all available patients. Whole-exome sequencing (WES) was performed on all probands and at least one of their parents. Bioinformatics analysis was performed to evaluate the pathogenicity of the candidate variants. Exon 4 of was amplified by polymerase chain reaction and directly sequenced. All patients underwent full ocular examinations. This was an observational study to explore the genotype-phenotype relationships in the four families with a common candidate variant.

RESULTS

Various ocular phenotypes were detected in these families, mainly including CCs, elongated axial length, and myopia-related fundus changes. The gene mutation, p.Arg130Cys, was detected in all patients. This was further confirmed by Sanger sequencing. The proportion of probands with this mutation in our CCs database was 3.1% (4/130), which indicated that this mutation appears to be a frequent cause of cataracts in the Han Chinese population. This variation has been reported by other investigators before and was correlated with isolated cataracts.

CONCLUSIONS

This is the first study that reports various ocular phenotypes associated with the p.Arg130Cys mutation in the gene, which indicated the phenotypic heterogeneity of this gene. might not only function as an integral membrane protein in lens fiber cells but also be associated with the axial development of the eyeball. Functional studies of the gene are important and should receive more attention.