Clinical and genetic analysis of a family affected with dominant optic atrophy (OPA1)

Jeremiah Brown Jr; John H Fingert; Chris M Taylor; Max Lake; Val C Sheffield; Edwin M Stone

doi:10.1001/archopht.1997.01100150097016

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Clinical and genetic analysis of a family affected with dominant optic atrophy (OPA1)

Journal article

Peer reviewed

Clinical and genetic analysis of a family affected with dominant optic atrophy (OPA1)

Jeremiah Brown Jr, John H Fingert, Chris M Taylor, Max Lake, Val C Sheffield and Edwin M Stone

Archives of ophthalmology (1960), Vol.115(1), pp.95-99

01/1997

DOI: 10.1001/archopht.1997.01100150097016

PMID: 9006432

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Abstract

To refine the dominant optic atrophy locus, OPA1, on chromosome 3q and to characterize the phenotype of a 6-generation family pedigree affected with this disease. Fifty-six family members had a complete eye examination. Clinical records of an additional 3 patients were reviewed. Goldmann perimetry and a 21-chip subtest of the Farnsworth-Munsell 100-Hue test were performed on selected patients. Affected patients, unaffected siblings, and potentially informative spouses were genotyped with short tandem repeat polymorphisms located on chromosome 3. The genotypic data were subjected to linkage analysis. Thirty-four family members were found to be clinically affected. Most experienced vision loss (20/40 or poorer) in the first decade of life. Most (9 of the 16 eyes) progressed to 20/800 or poorer visual acuity by age 60 years, while 2 patients maintained visual acuities of 20/40 at that age. Affected patients had a 2- to 10-fold increase in the error score of a 21-chip subtest of the Farnsworth-Munsell 100-Hue test compared with age-matched unaffected family members. The optic nerve examination revealed temporal pallor and excavation in all affected individuals. Linkage analysis revealed significant lod scores with 9 markers. The highest lod score, 10.1 (theta = 0) [corrected], was obtained with marker D3S2305. Analysis of recombinants narrowed the disease interval to approximately 3.8 centimorgans, flanked by D3S3669 (centromeric) and D3S1305 (telomeric). Most patients affected with dominant optic atrophy in this family progressed to legal blindness by middle age. Color vision testing is a sensitive method for detection of affected patients. The dominant optic atrophy locus, OPA1, has been refined by the identification of new flanking markers: D3S3669 (centromeric) and D3S1305 (telomeric).

Genetic Markers

Optic Nerve - pathology

Optic Atrophies, Hereditary - genetics

Humans

Middle Aged

Child, Preschool

Infant

Male

Color Vision Defects - genetics

Lod Score

Visual Fields

Aged, 80 and over

Adult

Female

Genetic Linkage - genetics

Optic Atrophies, Hereditary - diagnosis

Child

Infant, Newborn

Genotype

Chromosome Mapping

Visual Acuity

Blindness - genetics

Pedigree

Adolescent

Aged

Color Vision Defects - diagnosis

Visual Field Tests

Fundus Oculi

Chromosomes, Human, Pair 3 - genetics

Details

Title: Subtitle: Clinical and genetic analysis of a family affected with dominant optic atrophy (OPA1)
Creators: Jeremiah Brown Jr - Department of Ophthalmology, University of Iowa College of Medicine, Iowa City, USA
John H Fingert
Chris M Taylor
Max Lake
Val C Sheffield
Edwin M Stone
Resource Type: Journal article
Publication Details: Archives of ophthalmology (1960), Vol.115(1), pp.95-99
DOI: 10.1001/archopht.1997.01100150097016
PMID: 9006432
NLM abbreviation: Arch Ophthalmol
ISSN: 0003-9950
eISSN: 1538-3601
Publisher: American Medical Association; United States
Grant note: HG00457 / NHGRI NIH HHS EY10564 / NEI NIH HHS EY10539 / NEI NIH HHS
Language: English
Date published: 01/1997
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983979916202771

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