title: A novel MIP gene mutation associated with autosomal dominant congenital cataracts in a Chinese family.
abstract: BACKGROUND
  The major intrinsic protein gene (MIP), also known as MIP26 or AQP0, is a member of the water-transporting aquaporin family, which plays a critical role in the maintenance of lifelong lens transparency. To date, several mutations in MIP (OMIM 154050) have been linked to hereditary cataracts in humans. However, more pathogenic mutations remain to be identified. In this study, we describe a four-generation Chinese family with a nonsense mutation in MIP associated with an autosomal dominant congenital cataract (ADCC), thus expanding the mutational spectrum of this gene.
  
  
  METHODS
  A large four-generation Chinese family affected with typical Y-suture cataracts combined with punctuate cortical opacities and 100 ethnically matched controls were recruited. Genomic DNA was extracted from peripheral blood leukocytes to analyze congenital cataract-related candidate genes. Effects of the sequence change on the structure and function of proteins were predicted by bioinformatics analysis.
  
  
  RESULTS
  Direct sequencing of MIP in all affected members revealed a heterozygous nucleotide exchange c.337C>T predicting an arginine to a stop codon exchange (p.R113X). The substitution co-segregated well in all the affected individuals in the family and was not found in unaffected members or in the 100 unrelated healthy controls. Bioinformatics analysis predicted that the mutation affects the secondary structure and function of the MIP protein.
  
  
  CONCLUSIONS
  We identified a novel mutation of MIP (p.R113X) in a Chinese cataract family. This is the first nonsense mutation of MIP identified thus far. This novel mutation is also the first disease-causing mutation located in the loop C domain of MIP. The results add to the list of mutations of the MIP linked to cataracts.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Yu
authors.forename: Yinhui
authors.initials: Y
authors.lastname: Yu
authors.forename: Peiqing
authors.initials: P
authors.lastname: Chen
authors.forename: Jinyu
authors.initials: J
authors.lastname: Li
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, No,88 Jiefang Road, Hangzhou, 310009, China. xlren@zju.edu.cn.
authors.forename: Ke
authors.initials: K
authors.lastname: Yao
mesh_terms: D000328:Adult; D020346:Aquaporins / Q000737:chemistry / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D018389:Codon, Nonsense; D019295:Computational Biology; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D010375:Pedigree; D017433:Protein Structure, Secondary; D055815:Young Adult
chemical_list: D020346:Aquaporins; D018389:Codon, Nonsense; D005136:Eye Proteins; C030328:aquaporin 0