A spectrum of FOXC1 mutations suggests gene dosage as a mechanism for developmental defects of the anterior chamber of the eye

Darryl Y Nishimura; Charles C Searby; Wallace L Alward; David Walton; James E Craig; David A Mackey; Kazuhide Kawase; Adam B Kanis; Shivanand R Patil; Edwin M Stone; Val C Sheffield

doi:10.1086/318183

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A spectrum of FOXC1 mutations suggests gene dosage as a mechanism for developmental defects of the anterior chamber of the eye

Journal article

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A spectrum of FOXC1 mutations suggests gene dosage as a mechanism for developmental defects of the anterior chamber of the eye

Darryl Y Nishimura, Charles C Searby, Wallace L Alward, David Walton, James E Craig, David A Mackey, Kazuhide Kawase, Adam B Kanis, Shivanand R Patil, Edwin M Stone, …

American journal of human genetics, Vol.68(2), pp.364-372

02/2001

DOI: 10.1086/318183

PMCID: PMC1235270

PMID: 11170889

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Abstract

Mutations in the forkhead transcription-factor gene (FOXC1), have been shown to cause defects of the anterior chamber of the eye that are associated with developmental forms of glaucoma. Discovery of these mutations was greatly facilitated by the cloning and characterization of the 6p25 breakpoint in a patient with both congenital glaucoma and a balanced-translocation event involving chromosomes 6 and 13. Here we describe the identification of novel mutations in the FOXC1 gene in patients with anterior-chamber defects of the eye. We have detected nine new mutations (eight of which are novel) in the FOXC1 gene in patients with anterior-chamber eye defects. Of these mutations, five frameshift mutations predict loss of the forkhead domain, as a result of premature termination of translation. Of particular interest is the fact that two families have a duplication of 6p25, involving the FOXC1 gene. These data suggest that both FOXC1 haploinsufficiency and increased gene dosage can cause anterior-chamber defects of the eye.

Mutation

Gene Duplication

Physical Chromosome Mapping

Humans

Anterior Chamber - abnormalities

Molecular Sequence Data

Gene Dosage

Transcription Factors - genetics

Eye Abnormalities - genetics

Chromosomes, Human, Pair 6 - genetics

DNA - genetics

DNA - chemistry

DNA Mutational Analysis

Chromosome Aberrations

Forkhead Transcription Factors

DNA-Binding Proteins

Details

Title: Subtitle: A spectrum of FOXC1 mutations suggests gene dosage as a mechanism for developmental defects of the anterior chamber of the eye
Creators: Darryl Y Nishimura - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
Charles C Searby
Wallace L Alward
David Walton - Harvard Medical School
James E Craig - University of Tasmania
David A Mackey
Kazuhide Kawase
Adam B Kanis - University of Iowa
Shivanand R Patil
Edwin M Stone
Val C Sheffield
Resource Type: Journal article
Publication Details: American journal of human genetics, Vol.68(2), pp.364-372
DOI: 10.1086/318183
PMID: 11170889
PMCID: PMC1235270
NLM abbreviation: Am J Hum Genet
ISSN: 0002-9297
eISSN: 1537-6605
Publisher: United States
Grant note: R01-EY-10564 / NEI NIH HHS R01 EY010564 / NEI NIH HHS
Language: English
Date published: 02/2001
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983980080602771

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