title: Large Deletions of TSPAN12 Cause Familial Exudative Vitreoretinopathy (FEVR).
abstract: Familial exudative vitreoretinopathy (FEVR) is a rare, hereditary visual disorder. The gene TSPAN12 is associated with autosomal dominant inheritance of FEVR. The prevalence and impact of large deletions/duplications of TSPAN12 on FEVR patients is unknown. To glean better insight of TSPAN12 on FEVR pathology, herein, we describe three FEVR patients with TSPAN12 deletions.
  
  
  
  Thirty-three Korean FEVR patients, who previously screened negative for TSPAN12 mutations, mutations in other FEVR-associated genes such as NDP, FZD4, LRP5, and large deletions and duplications of NDP, FZD4, and LRP5, were selected for TSPAN12 large deletion and duplication analyses. Semiquantitative multiplex PCR for TSPAN12 gene dosage analyses were performed, followed by droplet digital PCR (ddPCR) for validation.
  
  
  
  Among the 33 patients, three patients were confirmed to carry large TSPAN12 deletions. Two of them had whole-gene deletions of TSPAN12, and the other patient possessed a deletion of TSPAN12 in exon 4. FEVR severity detected in these patients was not more severe than in a patient with TSPAN12 point mutation.
  
  
  
  Regarding previously reported proportions of FEVR-associated genes contributing to the disorder's autosomal dominant inheritance pattern in Korea, we determined that patients with TSPAN12 large deletions were more common than patients with single nucleotide variants in TSPAN12. Evaluating TSPAN12 large deletions and duplications should be considered in FEVR screening and diagnosis as well as in routine genetic workups for FEVR patients.
authors.affiliation: Department of Laboratory Medicine, Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Seo
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Man Jin
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sung Wook
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jeong Hun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Yu
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Song
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sung Im
authors.initials: SI
authors.lastname: Cho
authors.affiliation: Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Oh
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jee-Soo
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seungjun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Moon-Woo
authors.initials: MW
authors.lastname: Seong
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea 5Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
authors.forename: Sung Sup
authors.initials: SS
authors.lastname: Park
authors.affiliation: Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D015785:Eye Diseases, Hereditary; D000080345:Familial Exudative Vitreoretinopathies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D015995:Prevalence; D056910:Republic of Korea / Q000453:epidemiology; D012164:Retinal Diseases / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D017384:Sequence Deletion / Q000235:genetics*; D059470:Tetraspanins / Q000235:genetics* / Q000378:metabolism
chemical_list: C545100:TSPAN12 protein, human; D059470:Tetraspanins; D004247:DNA