title: Identification of a novel missense mutation of MIP in a Chinese family with congenital cataracts by target region capture sequencing.
abstract: Congenital cataract is both clinically diverse and genetically heterogeneous. To investigate the underlying genetic defect in three-generations of a Chinese family with autosomal dominant congenital cataracts, we recruited family members who underwent comprehensive ophthalmic examinations. A heterozygous missense mutation c.634G > C (p.G212R) substitution was identified in the MIP gene through target region capture sequencing. The prediction results of PolyPhen-2 and SIFT indicated that this mutation was likely to damage the structure and function of MIP. Confocal microscopy images showed that the intensity of the green fluorescent signal revealed much weaker signal from the mutant compared to the wild-type MIP. The expressed G212R-MIP was diminished and almost exclusively cytoplasmic in the HeLa cells; whereas the WT-MIP was stable dispersed throughout the cytoplasm, and it appeared to be in the membrane structure. Western blot analysis indicated that the protein expression level of the mutant form of MIP was remarkably reduced compared with that of the wild type, however, the mRNA levels of the wild-type and mutant cells were comparable. In conclusion, our study presented genetic and functional evidence for a novel MIP mutation of G212R, which leads to congenital progressive cortical punctate with or without Y suture.
authors.affiliation: Department of Ophthalmology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.|School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China.|Casey Eye Institute Molecular Diagnostic Laboratory, Portland, Oregon, USA.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Tongde Hospital of Zhejiang Province, Hangzhou, China.
authors.forename: Baisheng
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Hong
authors.affiliation: Division of Hematology-oncology, Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Cell Biology and Medical Genetics, Zhejiang University School of Medicine, Hangzhou, China.|Department of Pathology and Laboratory of Medicine, University of Rochester Medical Centre, Rochester, New York, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Qi
authors.affiliation: Department of Ophthalmology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Shen
mesh_terms: D020346:Aquaporins / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D002386:Cataract / Q000151:congenital* / Q000235:genetics* / Q000473:pathology; D002681:China; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D020346:Aquaporins; D005136:Eye Proteins; D012333:RNA, Messenger; C030328:aquaporin 0