Identification of a novel MIP frameshift mutation associated with congenital cataract in a Chinese family by whole-exome sequencing and functional analysis. Academic Article uri icon

Overview

abstract

  • PURPOSE: To detect the underlying pathogenesis of congenital cataract in a four-generation Chinese family. METHODS: Whole-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. RESULTS: The 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. CONCLUSIONS: Our 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.

publication date

  • April 26, 2018

Research

keywords

  • Aquaporins
  • Cataract
  • Eye Proteins
  • Frameshift Mutation

Identity

PubMed Central ID

  • PMC6085365

Scopus Document Identifier

  • 85046007575

Digital Object Identifier (DOI)

  • 10.1016/j.bbagen.2014.05.002

PubMed ID

  • 29695758

Additional Document Info

volume

  • 32

issue

  • 8