PUBLICATION

Mutation of IPO13 causes recessive ocular coloboma, microphthalmia, and cataract

Authors
Huang, X.F., Xiang, L., Cheng, W., Cheng, F.F., He, K.W., Zhang, B.W., Zheng, S.S., Han, R.Y., Zheng, Y.H., Xu, X.T., Yu, H.Y., Zhuang, W., Leung, Y.F., Jin, Z.B.
ID
ZDB-PUB-180428-4
Date
2018
Source
Experimental & molecular medicine   50: 53 (Journal)
Registered Authors
Leung, Yuk Fai
Keywords
none
MeSH Terms
  • Adult
  • Animals
  • Cataract/genetics*
  • Coloboma/genetics*
  • Disease Models, Animal
  • Gene Knockdown Techniques
  • Humans
  • Karyopherins/genetics*
  • Male
  • Mice
  • Microphthalmos/genetics*
  • Models, Molecular
  • Point Mutation*
  • Transcriptome
  • Zebrafish/genetics*
PubMed
29700284 Full text @ Exp. Mol. Med.
Abstract
Ocular coloboma is a developmental structural defect of the eye that often occurs as complex ocular anomalies. However, its genetic etiology remains largely unexplored. Here we report the identification of mutation (c.331C>T, p.R111C) in the IPO13 gene in a consanguineous family with ocular coloboma, microphthalmia, and cataract by a combination of whole-exome sequencing and homozygosity mapping. IPO13 encodes an importin-B family protein and has been proven to be associated with the pathogenesis of coloboma and microphthalmia. We found that Ipo13 was expressed in the cornea, sclera, lens, and retina in mice. Additionally, the mRNA expression level of Ipo13 decreased significantly in the patient compared with its expression in a healthy individual. Morpholino-oligonucleotide-induced knockdown of ipo13 in zebrafish caused dose-dependent microphthalmia and coloboma, which is highly similar to the ocular phenotypes in the patient. Moreover, both visual motor response and optokinetic response were impaired severely. Notably, these ocular phenotypes in ipo13-deficient zebrafish could be rescued remarkably by full-length ipo13 mRNA, suggesting that the phenotypes observed in zebrafish were due to insufficient ipo13 function. Altogether, our findings demonstrate, for the first time, a new role of IPO13 in eye morphogenesis and that loss of function of IPO13 could lead to ocular coloboma, microphthalmia, and cataract in humans and zebrafish.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes