title: KIF11 mutations are a common cause of autosomal dominant familial exudative vitreoretinopathy.
abstract: OBJECTIVE
  To identify KIF11 mutations in patients with familial exudative vitreoretinopathy (FEVR) and to describe the associated phenotypes.
  
  
  METHODS
  Mutation analysis in a cohort of patients in a single institute was conducted. Bioinformatics was performed for whole exome sequencing, and the variants were confirmed by Sanger sequencing. Clinical data and DNA samples were collected from 814 unrelated Chinese probands, including 34 with FEVR, at the Pediatric and Genetic Eye Clinic, Zhongshan Ophthalmic Centre, Guangzhou, China.
  
  
  RESULTS
  Four novel heterozygous truncation mutations in KIF11, including c.131_132dupAT (p.P45Ifs*92), c.2230C>T (p.Q744*), c.2863C>T (p.Q955*) and c.2952_2955delGCAG (p.G985Ifs*6), were detected in four of 34 probands with FEVR. Combined with our previously identified mutations in FEVR cases (n=14), KIF11 mutations were identified in 8.3% (4/48) of all probands with FEVR. Ocular phenotypes documented in patients with KIF11 mutations showed a significant great variability of FEVR from the avascular zone in the peripheral retina to bilateral complete retinal detachment. Analysis of available family members in family QT1314 and QT937 showed segregation of KIF11 mutations with the phenotype of FEVR as expected. The family QT964 with two affected siblings and unaffected parents demonstrated a peculiar somatic mosaicism in the mother who had a low copy number variant (about 7% in her leucocyte DNA).
  
  
  CONCLUSIONS
  Identification of mutations in 8.3% patients suggests KIF11 mutations as a common cause of FEVR. Patients with KIF11 mutations showed typical, but variable, signs of FEVR with or without microcephaly, lymphoedema and mental retardation.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-sen University, Guangzhou, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xueshan
authors.initials: X
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-sen University, Guangzhou, China.
authors.forename: Qingjiong
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000328:Adult; D002648:Child; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D059472:Exome / Q000235:genetics; D015785:Eye Diseases, Hereditary; D000080345:Familial Exudative Vitreoretinopathies; D005260:Female; D005451:Fluorescein Angiography; D016368:Frameshift Mutation; D060005:Genotyping Techniques; D006801:Humans; D016547:Kinesins / Q000235:genetics*; D008297:Male; D009030:Mosaicism; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012164:Retinal Diseases / Q000175:diagnosis / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D017931:DNA Primers; C470243:KIF11 protein, human; D016547:Kinesins