Familial Cavitary Optic Disk Anomalies: Identification of a Novel Genetic Locus

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

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Purpose: 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. Design: Linkage analysis of a pedigree affected with cavitary optic disk anomalies. Methods: 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. Results: 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 (θ = 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. Conclusions: 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).

Original languageEnglish (US)
JournalAmerican Journal of Ophthalmology
Volume143
Issue number5
DOIs
StatePublished - May 1 2007
Externally publishedYes

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Genetic Loci
Genes
Pedigree
Microsatellite Repeats
Single Nucleotide Polymorphism
Chromosomes
Low Tension Glaucoma
Optic Nerve Diseases
Optic Disk
Genotype
Cavitary Optic Disc Anomalies
Mutation

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Fingert, J. H., Honkanen, R. A., Shankar, S., Affatigato, L. M., Ehlinger, M. A., Moore, M. D., ... Alward, W. L. M. (2007). Familial Cavitary Optic Disk Anomalies: Identification of a Novel Genetic Locus. American Journal of Ophthalmology, 143(5). https://doi.org/10.1016/j.ajo.2007.01.042

Familial Cavitary Optic Disk Anomalies : Identification of a Novel Genetic Locus. / Fingert, John H.; Honkanen, Robert A.; Shankar, Suma; Affatigato, Louisa M.; Ehlinger, Mary A.; Moore, Michael D.; Jampol, Lee M.; Sheffield, Val C.; Stone, Edwin M.; Alward, Wallace L.M.

In: American Journal of Ophthalmology, Vol. 143, No. 5, 01.05.2007.

Research output: Contribution to journalArticle

Fingert, JH, Honkanen, RA, Shankar, S, Affatigato, LM, Ehlinger, MA, Moore, MD, Jampol, LM, Sheffield, VC, Stone, EM & Alward, WLM 2007, 'Familial Cavitary Optic Disk Anomalies: Identification of a Novel Genetic Locus', American Journal of Ophthalmology, vol. 143, no. 5. https://doi.org/10.1016/j.ajo.2007.01.042
Fingert, John H. ; Honkanen, Robert A. ; Shankar, Suma ; Affatigato, Louisa M. ; Ehlinger, Mary A. ; Moore, Michael D. ; Jampol, Lee M. ; Sheffield, Val C. ; Stone, Edwin M. ; Alward, Wallace L.M. / Familial Cavitary Optic Disk Anomalies : Identification of a Novel Genetic Locus. In: American Journal of Ophthalmology. 2007 ; Vol. 143, No. 5.
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