Familial cavitary optic disk anomalies: identification of a novel genetic locus

John H Fingert; Robert A Honkanen; Suma P Shankar; Louisa M Affatigato; Mary A Ehlinger; Michael D Moore; Lee M Jampol; Val C Sheffield; Edwin M Stone; Wallace L M Alward

doi:10.1016/j.ajo.2007.01.042

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Familial cavitary optic disk anomalies: identification of a novel genetic locus

Journal article

Peer reviewed

Familial cavitary optic disk anomalies: identification of a novel genetic locus

John H Fingert, Robert A Honkanen, Suma P Shankar, Louisa M Affatigato, Mary A Ehlinger, Michael D Moore, Lee M Jampol, Val C Sheffield, Edwin M Stone and Wallace L M Alward

American journal of ophthalmology, Vol.143(5), pp.795-800.e1

05/2007

DOI: 10.1016/j.ajo.2007.01.042

PMCID: PMC3684050

PMID: 17368552

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Abstract

To identify the chromosomal location of the gene involved in the pathogenesis of cavitary optic disk anomalies in a large pedigree with autosomal dominant inheritance of disease. Linkage analysis of a pedigree affected with cavitary optic disk anomalies. Optic disk photographs were examined for the presence of cavitary optic disk anomalies. Sixteen affected family members and one obligate carrier were identified and studied with linkage analysis using both microarrays of single nucleotide polymorphisms (SNPs) and short tandem repeat polymorphism (STRP) markers. Multipoint linkage analysis of SNP genotypes yielded a maximum nonparametric logarithm of the odds (LOD) score of 21.7 with markers located on chromosome 12q. Linkage was confirmed with 16 STRP markers in the 12q region. A maximum two-point LOD score of 4.06 (theta = 0) was obtained with marker D12S1700. The disease interval defined by observed recombinants is 9.1 cM, which corresponds to 13.5 Mbp. Three candidate genes (GDF-11, NEUROD4, and WIF1) in the chromosome 12q locus were evaluated as possible disease-causing genes. No mutations were detected in the coding sequence of these genes. The discovery of the chromosomal location of a gene responsible for cavitary optic disk anomalies is a key step in identifying the genetic basis of this condition and ultimately may provide important insight into the pathogenesis of more common optic nerve diseases such as normal-tension glaucoma and primary open-angle glaucoma (POAG).

Genetic Markers

Oligonucleotide Array Sequence Analysis

Humans

Middle Aged

Child, Preschool

Male

Growth Differentiation Factors

Adult

Female

Bone Morphogenetic Proteins - genetics

Child

Chromosomes, Human, Pair 12 - genetics

Microsatellite Repeats

Genetic Linkage

Optic Disk - abnormalities

Repressor Proteins - genetics

Eye Abnormalities - genetics

Optic Disk - blood supply

Nerve Tissue Proteins - genetics

Optic Nerve Diseases - genetics

Pedigree

Adaptor Proteins, Signal Transducing - genetics

Adolescent

Aged

Polymorphism, Single Nucleotide

Details

Title: Subtitle: Familial cavitary optic disk anomalies: identification of a novel genetic locus
Creators: John H Fingert - Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA
Robert A Honkanen
Suma P Shankar
Louisa M Affatigato
Mary A Ehlinger
Michael D Moore
Lee M Jampol
Val C Sheffield
Edwin M Stone
Wallace L M Alward
Resource Type: Journal article
Publication Details: American journal of ophthalmology, Vol.143(5), pp.795-800.e1
DOI: 10.1016/j.ajo.2007.01.042
PMID: 17368552
PMCID: PMC3684050
NLM abbreviation: Am J Ophthalmol
ISSN: 0002-9394
eISSN: 1879-1891
Publisher: United States
Grant note: R01 EY010564-07 / NEI NIH HHS 2R01EY010564-11A1 / NEI NIH HHS R01 EY010564 / NEI NIH HHS
Language: English
Date published: 05/2007
Academic Unit: Stead Family Department of Pediatrics; The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983979963702771

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