title: Ocular Phenotype of a Family with FAM161A-associated Retinal Degeneration.
abstract: BACKGROUND
  Characterization of retinal degeneration (RD) using high-resolution retinal imaging and exome sequencing may identify phenotypic features that correspond with specific genetic defects.
  
  
  METHODS
  Six members from a non-consanguineous Indian family (three affected siblings, their asymptomatic parents and an asymptomatic child) were characterized clinically, using visual acuity, perimetry, full-field electroretinography (ERG), optical coherence tomography and cone structure as outcome measures. Cone photoreceptors were imaged in the proband using adaptive optics scanning laser ophthalmoscopy. The exome was captured using Nimblegen SeqCap EZ V3.0 probes and sequenced using lllumina HiSeq. Reads were mapped to reference hg19. Confirmation of variants and segregation analysis was performed using dideoxy sequencing.
  
  
  RESULTS
  Analysis of exome variants using exomeSuite identified five homozygous variants in four genes known to be associated with RD. Further analysis revealed a homozygous nonsense mutation, c.1105 C > T, p.Arg335Ter, in the FAM161A gene segregating with RD. Three additional variants were found to occur at high frequency. Affected members showed a range of disease severity beginning at different ages, but all developed severe visual field and outer retinal loss.
  
  
  CONCLUSIONS
  Exome analysis revealed a nonsense homozygous mutation in FAM161A segregating with RD with severe vision loss and a range of disease onset and progression. Loss of outer retinal structures demonstrated with high-resolution retinal imaging suggests FAM161A is important for normal photoreceptor structure and survival. Exome sequencing may identify causative genetic variants in autosomal recessive RD families when other genetic test strategies fail to identify a mutation.
authors.affiliation: a Department of Ophthalmology , University of California , San Francisco , CA , USA .
authors.forename: Jacque L
authors.initials: JL
authors.lastname: Duncan
authors.affiliation: b Shiley Eye Center, University of California , San Diego , La Jolla , CA , USA .
authors.forename: Pooja
authors.initials: P
authors.lastname: Biswas
authors.affiliation: b Shiley Eye Center, University of California , San Diego , La Jolla , CA , USA .
authors.forename: Igor
authors.initials: I
authors.lastname: Kozak
authors.affiliation: b Shiley Eye Center, University of California , San Diego , La Jolla , CA , USA .
authors.forename: Mili
authors.initials: M
authors.lastname: Navani
authors.affiliation: a Department of Ophthalmology , University of California , San Francisco , CA , USA .
authors.forename: Reema
authors.initials: R
authors.lastname: Syed
authors.affiliation: a Department of Ophthalmology , University of California , San Francisco , CA , USA .
authors.forename: Shiri
authors.initials: S
authors.lastname: Soudry
authors.affiliation: a Department of Ophthalmology , University of California , San Francisco , CA , USA .
authors.forename: Moreno
authors.initials: M
authors.lastname: Menghini
authors.affiliation: c National Eye Institute, NIH , Bethesda , MD , USA .|d Princeton Neuroscience Institute, Princeton University , Princeton , NJ , USA .
authors.forename: Rafael C
authors.initials: RC
authors.lastname: Caruso
authors.affiliation: c National Eye Institute, NIH , Bethesda , MD , USA .
authors.forename: Brett G
authors.initials: BG
authors.lastname: Jeffrey
authors.affiliation: e Department of Ophthalmology , University of Michigan , Ann Arbor , MI , USA .
authors.forename: John R
authors.initials: JR
authors.lastname: Heckenlively
authors.affiliation: f National Institute of Nutrition, Indian Council of Medical Research , Hyderabad , India .
authors.forename: G Bhanuprakash
authors.initials: GB
authors.lastname: Reddy
authors.affiliation: b Shiley Eye Center, University of California , San Diego , La Jolla , CA , USA .|g Department of Molecular and Experimental Medicine , The Scripps Research Institute , La Jolla , CA , USA , and.
authors.forename: Pauline
authors.initials: P
authors.lastname: Lee
authors.affiliation: h School of Optometry and Vision Science Graduate Group, University of California , Berkeley , CA , USA.
authors.forename: Austin
authors.initials: A
authors.lastname: Roorda
authors.affiliation: b Shiley Eye Center, University of California , San Diego , La Jolla , CA , USA .
authors.forename: Radha
authors.initials: R
authors.lastname: Ayyagari
mesh_terms: D000328:Adult; D000368:Aged; D001766:Blindness / Q000235:genetics; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D004596:Electroretinography; D059472:Exome / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D058609:Visual Field Tests; D014794:Visual Fields / Q000502:physiology
chemical_list: D018389:Codon, Nonsense; D005136:Eye Proteins; C552553:FAM161A protein, human
keywords: Exome sequencing; FAM161A; retinal degeneration