title: Value of whole exome sequencing for syndromic retinal dystrophy diagnosis in young patients.
abstract: BACKGROUND
  Several retinal dystrophies are associated with syndromic features including such conditions as Bardet-Biedl and Joubert syndromes. Cohen syndrome is an autosomal recessive disorder associated with multiple clinical manifestations including developmental delay, acquired microcephaly, myopia, pigmentary retinopathy, joint hypermobility, truncal obesity, friendly disposition and intermittent neutropenia. In young patients, diagnosis is difficult, because several of the characteristic features may not be present until school age or later years and the intermittent neutropenia is not always detectable.
  
  
  METHODS
  This was a prospective study using whole exome sequencing in syndromic retinal dystrophy. It was undertaken in a hospital and research institute setting.
  
  
  METHODS
  Participants in this study were members of a consanguineous Australian family of Lebanese ethnicity with two siblings with retinal dystrophy, microcephaly and developmental delay.
  
  
  METHODS
  Detailed clinical evaluation was undertaken. Whole exome capture and sequencing of patient genomic DNA samples was followed by sequence alignment, variant detection, comparison and prioritization.
  
  
  METHODS
  Pathogenic variant identification in the disease-causing gene in affected individuals.
  
  
  RESULTS
  We identified a novel homozygous deletion leading to a frameshift mutation in VPS13B, c.11327del, p.(Asn3776Thrfs*102), the disease gene associated with Cohen syndrome.
  
  
  CONCLUSIONS
  This report emphasizes the value of a broad-based whole exome sequencing approach in disease gene identification in the syndromic retinal dystrophies, where all disease characteristics may not be present in young patients to allow a clinical diagnosis. This facilitates improved prognostic and genetic information for patients and families.
authors: Eye and Developmental Genetics Research Group, The Children's Hospital at Westmead, Sydney, New South Wales, Australia; Eye Genetics Group, Children's Medical Research Institute, Sydney, New South Wales, Australia.
authors: Ivan
authors: I
authors: Prokudin
authors: Dong
authors: D
authors: Li
authors: Sijie
authors: S
authors: He
authors: Yiran
authors: Y
authors: Guo
authors: Linda
authors: L
authors: Goodwin
authors: Meredith
authors: M
authors: Wilson
authors: Loreto
authors: L
authors: Rose
authors: Lifeng
authors: L
authors: Tian
authors: Yulan
authors: Y
authors: Chen
authors: Jinlong
authors: J
authors: Liang
authors: Brendan
authors: B
authors: Keating
authors: Xun
authors: X
authors: Xu
authors: Robyn V
authors: RV
authors: Jamieson
authors: Hakon
authors: H
authors: Hakonarson
mesh_terms: D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics; D059472:Exome / Q000235:genetics*; D005260:Female; D005385:Fingers / Q000002:abnormalities*; D016368:Frameshift Mutation; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008831:Microcephaly / Q000175:diagnosis* / Q000235:genetics; D009123:Muscle Hypotonia / Q000175:diagnosis* / Q000235:genetics; D009216:Myopia / Q000175:diagnosis* / Q000235:genetics; D009765:Obesity / Q000175:diagnosis* / Q000235:genetics; D010375:Pedigree; D011446:Prospective Studies; D012162:Retinal Degeneration; D058499:Retinal Dystrophies / Q000175:diagnosis* / Q000235:genetics; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D035781:Siblings; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: C475722:VPS13B protein, human; D033921:Vesicular Transport Proteins
keywords: Cohen syndrome; VPS13B; whole exome sequencing