Abstract
PurposeTo detect the underlying pathogenesis of congenital cataract in a four-generation Chinese family.MethodsWhole-exome sequencing (WES) of family members (III:4, IV:4, and IV:6) was performed. Sanger sequencing and bioinformatics analysis were subsequently conducted. Full-length WT-MIP or K228fs-MIP fused to HA markers at the N-terminal was transfected into HeLa cells. Next, quantitative real-time PCR, western blotting and immunofluorescence confocal laser scanning were performed.ResultsThe age of onset for nonsyndromic cataracts in male patients was by 1-year old, earlier than for female patients, who exhibited onset at adulthood. A novel c.682_683delAA (p.K228fs230X) mutation in main intrinsic protein (MIP) cosegregated with the cataract phenotype. The instability index and unfolded states for truncated MIP were predicted to increase by bioinformatics analysis. The mRNA transcription level of K228fs-MIP was reduced compared with that of WT-MIP, and K228fs-MIP protein expression was also lower than that of WT-MIP. Immunofluorescence images showed that WT-MIP principally localized to the plasma membrane, whereas the mutant protein was trapped in the cytoplasm.ConclusionsOur study generated genetic and primary functional evidence for a novel c.682_683delAA mutation in MIP that expands the variant spectrum of MIP and help us better understand the molecular basis of cataract.
Highlights
Congenital cataract is a highly clinically and genetically heterogeneous disorder
Some main intrinsic protein (MIP) mutations linked to congenital cataracts have been identified in mice and humans, the heterogeneous phenotypes observed imply an intricate mechanism for MIP function
A four-generation family living in Hunan Province, China, was recruited, and members of the family were diagnosed with nonsyndromic congenital cataract (Fig. 1a)
Summary
Congenital cataract is a highly clinically and genetically heterogeneous disorder. Some main intrinsic protein (MIP) mutations linked to congenital cataracts have been identified in mice and humans, the heterogeneous phenotypes observed imply an intricate mechanism for MIP function. MIP is an intrinsic membrane protein that constitutes over 45% of the total membrane protein in lens fiber cells [1]. As a water channel protein, MIP plays an important role in the transportation of water and small neutral solutes [2,3,4]. MIP plays an important role in cell-to-cell adhesion in lens fiber cells [6, 7]. The detailed mechanisms underlying specific mutations remain hidden behind phenotypic heterogeneity, requiring further research
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
