A novel de novo CAPN5 mutation in a patient with inflammatory vitreoretinopathy, hearing loss, and developmental delay

Gabriel Velez; Alexander G Bassuk; Kellie A Schaefer; Brian Brooks; Lokesh Gakhar; MaryAnn Mahajan; Philip Kahn; Stephen H Tsang; Polly J Ferguson; Vinit B Mahajan

doi:10.1101/mcs.a002519

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A novel de novo CAPN5 mutation in a patient with inflammatory vitreoretinopathy, hearing loss, and developmental delay

Journal article

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Peer reviewed

A novel de novo CAPN5 mutation in a patient with inflammatory vitreoretinopathy, hearing loss, and developmental delay

Gabriel Velez, Alexander G Bassuk, Kellie A Schaefer, Brian Brooks, Lokesh Gakhar, MaryAnn Mahajan, Philip Kahn, Stephen H Tsang, Polly J Ferguson and Vinit B Mahajan

Cold Spring Harbor molecular case studies, Vol.4(3), p.a002519

06/2018

DOI: 10.1101/mcs.a002519

PMCID: PMC5983175

PMID: 29472286

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https://doi.org/10.1101/mcs.a002519View

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Abstract

Mutations that activate the protease calpain-5 ( cause a nonsyndromic adult-onset autoinflammatory eye disease characterized by uveitis, altered synaptic signaling, retinal degeneration, neovascularization, and intraocular fibrosis. We describe a pediatric patient with severe inflammatory vitreoretinopathy accompanied by hearing loss and developmental delay associated with a novel, de novo missense mutation (c.865C>T, p.Arg289Trp) that shows greater hyperactivation of the calpain protease, indicating a genotype-phenotype correlation that links mutation severity to proteolytic activity and the possibility of earlier onset syndromic disease with auditory and neurological abnormalities.

Electroencephalography

Phenotype

Mutation

Amino Acid Sequence

Hearing Loss - diagnosis

Genetic Association Studies

Humans

Child, Preschool

Models, Molecular

Vitreoretinopathy, Proliferative - diagnosis

Genotype

Male

Developmental Disabilities - genetics

Calpain - genetics

Calpain - chemistry

Whole Exome Sequencing

Hearing Loss - genetics

Vitreoretinopathy, Proliferative - genetics

Pedigree

Alleles

Protein Conformation

Developmental Disabilities - diagnosis

Details

Title: Subtitle: A novel de novo CAPN5 mutation in a patient with inflammatory vitreoretinopathy, hearing loss, and developmental delay
Creators: Gabriel Velez - Medical Scientist Training Program, University of Iowa, Iowa City, Iowa 52242, USA
Alexander G Bassuk - Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USA
Kellie A Schaefer - Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California 94304, USA
Brian Brooks - Pediatric, Developmental, and Genetic Eye Disease Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Lokesh Gakhar - Protein Crystallography Facility, University of Iowa, Iowa City, Iowa 52242, USA
MaryAnn Mahajan - Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California 94304, USA
Philip Kahn - Department of Pediatrics, Division of Pediatric Rheumatology, New York University, New York, New York 10016, USA
Stephen H Tsang - Department of Pathology & Cell Biology, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA
Polly J Ferguson - Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USA
Vinit B Mahajan - Palo Alto Veterans Administration, Palo Alto, California 94538, USA
Resource Type: Journal article
Publication Details: Cold Spring Harbor molecular case studies, Vol.4(3), p.a002519
DOI: 10.1101/mcs.a002519
PMID: 29472286
PMCID: PMC5983175
NLM abbreviation: Cold Spring Harb Mol Case Stud
ISSN: 2373-2865
eISSN: 2373-2873
Publisher: United States
Grant note: P30 EY026877 / NEI NIH HHS R01 EY018213 / NEI NIH HHS T32 GM007337 / NIGMS NIH HHS R01 AR059703 / NIAMS NIH HHS R01 EY026682 / NEI NIH HHS R01 EY024665 / NEI NIH HHS R21 AG050437 / NIA NIH HHS R01 EY025225 / NEI NIH HHS P30 CA013696 / NCI NIH HHS R01 EY024698 / NEI NIH HHS F30 EY027986 / NEI NIH HHS F31 EY026789 / NEI NIH HHS P30 EY019007 / NEI NIH HHS
Language: English
Date published: 06/2018
Academic Unit: Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Rheumatology, Allergy, and Immunology; Biochemistry and Molecular Biology; Neurology (Pediatrics); Medicine Administration
Record Identifier: 9984070155202771

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