title: TULP1 mutations causing early-onset retinal degeneration: preserved but insensitive macular cones.
abstract: OBJECTIVE
  To investigate visual function and outer and inner retinal structure in the rare form of retinal degeneration (RD) caused by TULP1 (tubby-like protein 1) mutations.
  
  
  METHODS
  Retinal degeneration patients with TULP1 mutations (n = 5; age range, 5-36 years) were studied by kinetic and chromatic static perimetry, en face autofluorescence imaging, and spectral-domain optical coherence tomography (OCT) scans. Outer and inner retinal laminar thickness were measured and mapped across the central retina. Comparisons were made with results from patients with RD associated with four ciliopathy genotypes (MAK, RPGR, BBS1, and USH2A).
  
  
  RESULTS
  The TULP1-RD patients were severely affected already in the first decade of life and there was rapidly progressive visual loss. No evidence of rod function was present at any age. Small central islands showed melanized retinal pigment epithelium by autofluorescence imaging and well-preserved photoreceptor laminar thickness by OCT imaging. There was extracentral loss of laminar architecture and increased inner retinal thickening. Structure-function relationships in residual foveal cone islands were made in TULP1-RD patients and in other retinopathies considered ciliopathies. Patients with TULP1-RD, unlike the others, had greater dysfunction for the degree of foveal structural preservation.
  
  
  CONCLUSIONS
  Retinal degeneration with TULP1 mutations leads to a small central island of residual foveal cones at early ages. These cones are less sensitive than expected from the residual structure. The human phenotype is consistent with experimental evidence in the Tulp1 knockout mouse model that visual dysfunction could be complicated by abnormal processes proximal to cone outer segments.
authors: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors: Samuel G
authors: SG
authors: Jacobson
authors: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors: Artur V
authors: AV
authors: Cideciyan
authors: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors: Wei Chieh
authors: WC
authors: Huang
authors: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors: Alexander
authors: A
authors: Sumaroka
authors: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors: Alejandro J
authors: AJ
authors: Roman
authors: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors: Sharon B
authors: SB
authors: Schwartz
authors: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors: Xunda
authors: X
authors: Luo
authors: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors: Rebecca
authors: R
authors: Sheplock
authors: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors: Joanna M
authors: JM
authors: Dauber
authors: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors: Malgorzata
authors: M
authors: Swider
authors: Department of Ophthalmology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States Howard Hughes Medical Institute, Iowa City, Iowa, United States.
authors: Edwin M
authors: EM
authors: Stone
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D055211:Retinal Photoreceptor Cell Inner Segment / Q000502:physiology; D055214:Retinal Photoreceptor Cell Outer Segment / Q000502:physiology; D041623:Tomography, Optical Coherence; D058609:Visual Field Tests; D014794:Visual Fields / Q000502:physiology; D055815:Young Adult
chemical_list: D005136:Eye Proteins; C105443:TULP1 protein, human
keywords: Leber congenital amaurosis; cilia; cone; optical coherence tomography; rod