Abstract
Congenital cataracts (CCs) have significant genotypic and phenotypic heterogeneity. The major intrinsic protein (MIP) gene, one of the causative genes of CCs, plays a vital role in maintaining the homeostasis and transparency of the lens. In this study, we identified a unique phenotype of anterior umbilication of the lens in a four-generation pedigree with CCs. All patients in the observed family had nystagmus, nuclear cataracts, and elongated axial lengths compared with their healthy counterparts except for patient I:2, whose axial length was unavailable, and patientII:4, who had total cataracts. We confirmed, using Sanger sequencing based on whole-exon sequencing (WES) data, that all patients carried a heterozygous variant NM_012064.4:c.97C > T (NP_036196.1:p.R33C) in their MIP gene. To our knowledge, 29 variants of the human MIP gene and the relative phenotypes associated with CCs have been identified. Nevertheless, this is the first report on the anterior umbilication of the lens with nuclear or total opacity caused by the c.97C > T (p.R33C) variant in the MIP gene. These results also provide evidence that the elongated axial length might be associated with this variant. This study further confirms the phenotypic heterogeneity of CCs.