TULP1 mutations causing early-onset retinal degeneration: preserved but insensitive macular cones

Samuel G Jacobson; Artur V Cideciyan; Wei Chieh Huang; Alexander Sumaroka; Alejandro J Roman; Sharon B Schwartz; Xunda Luo; Rebecca Sheplock; Joanna M Dauber; Malgorzata Swider; Edwin M Stone

doi:10.1167/iovs.14-14570

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TULP1 mutations causing early-onset retinal degeneration: preserved but insensitive macular cones

Journal article

Open access

Peer reviewed

TULP1 mutations causing early-onset retinal degeneration: preserved but insensitive macular cones

Samuel G Jacobson, Artur V Cideciyan, Wei Chieh Huang, Alexander Sumaroka, Alejandro J Roman, Sharon B Schwartz, Xunda Luo, Rebecca Sheplock, Joanna M Dauber, Malgorzata Swider, …

Investigative ophthalmology & visual science, Vol.55(8), pp.5354-5364

07/29/2014

DOI: 10.1167/iovs.14-14570

PMCID: PMC4580213

PMID: 25074776

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Abstract

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. 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). 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. 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.

Visual Fields - physiology

Retinal Degeneration - genetics

Tomography, Optical Coherence

Humans

Child, Preschool

Male

Retinal Degeneration - physiopathology

Young Adult

Retinal Photoreceptor Cell Outer Segment - physiology

Adolescent

Age of Onset

Adult

Female

Visual Field Tests

Eye Proteins - genetics

Retinal Degeneration - pathology

Child

Retinal Photoreceptor Cell Inner Segment - physiology

Details

Title: Subtitle: TULP1 mutations causing early-onset retinal degeneration: preserved but insensitive macular cones
Creators: Samuel G Jacobson - Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Artur V Cideciyan - Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Wei Chieh Huang - Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Alexander Sumaroka - Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Alejandro J Roman - Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Sharon B Schwartz - Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Xunda Luo - Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Rebecca Sheplock - Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Joanna M Dauber - Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Malgorzata Swider - Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Edwin M Stone - Department of Ophthalmology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States Howard Hughes Medical Institute, Iowa City, Iowa, United States
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.55(8), pp.5354-5364
DOI: 10.1167/iovs.14-14570
PMID: 25074776
PMCID: PMC4580213
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Grant note: R01 EY017549 / NEI NIH HHS P30 EY001583 / NEI NIH HHS
Language: English
Date published: 07/29/2014
Academic Unit: Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983980045102771

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