Association of a novel mutation in the retinol dehydrogenase 12 (RDH12) gene with autosomal dominant retinitis pigmentosa

John H Fingert; Kean Oh; Mina Chung; Todd E Scheetz; Jeaneen L Andorf; Rebecca M Johnson; Val C Sheffield; Edwin M Stone

doi:10.1001/archopht.126.9.1301

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Association of a novel mutation in the retinol dehydrogenase 12 (RDH12) gene with autosomal dominant retinitis pigmentosa

Journal article

Open access

Peer reviewed

Association of a novel mutation in the retinol dehydrogenase 12 (RDH12) gene with autosomal dominant retinitis pigmentosa

John H Fingert, Kean Oh, Mina Chung, Todd E Scheetz, Jeaneen L Andorf, Rebecca M Johnson, Val C Sheffield and Edwin M Stone

Archives of ophthalmology (1960), Vol.126(9), pp.1301-1307

09/2008

DOI: 10.1001/archopht.126.9.1301

PMID: 18779497

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Abstract

To identify the gene causing retinitis pigmentosa (RP) in an autosomal dominant pedigree. Family members with RP were studied with linkage analysis using single-nucleotide polymorphism and short tandem repeat polymorphic markers. Candidate genes in the linked region were evaluated with DNA sequencing. Nineteen family members had a mild form of RP. Multipoint linkage analysis of single-nucleotide polymorphism genotypes yielded a maximum nonparametric linkage score of 19.97 with markers located on chromosome 14q. LOD scores higher than 3.0 were obtained with 20 short tandem repeat polymorphic markers, and recombinants defined a 21.7-centimorgan locus on chromosome 14q. The retinol dehydrogenase 12 (RDH12) gene lies within this locus and was evaluated as a candidate gene. A frameshift mutation (776delG) was detected in all affected family members and was not detected in 158 control subjects. Heterozygous mutations in RDH12 can cause autosomal dominant RP with a late onset and relatively mild severity. This phenotype is dramatically different from the other disease associated with mutation in this gene, autosomal recessive Leber congenital amaurosis. The demonstration that mutations in a gene previously associated with recessive Leber congenital amaurosis can also cause dominant RP illustrates the wide phenotypic variability of retinal degeneration genes.

Electroretinography

Frameshift Mutation

Humans

Retinitis Pigmentosa - genetics

Genotype

Male

Chromosome Mapping

Lod Score

Retinitis Pigmentosa - diagnosis

Alcohol Oxidoreductases - genetics

Genes, Dominant

Pedigree

Adolescent

Polymerase Chain Reaction

Adult

Female

Polymorphism, Single Nucleotide

Visual Field Tests

Child

Chromosomes, Human, Pair 14 - genetics

Details

Title: Subtitle: Association of a novel mutation in the retinol dehydrogenase 12 (RDH12) gene with autosomal dominant retinitis pigmentosa
Creators: John H Fingert - Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Kean Oh
Mina Chung
Todd E Scheetz
Jeaneen L Andorf
Rebecca M Johnson
Val C Sheffield
Edwin M Stone
Resource Type: Journal article
Publication Details: Archives of ophthalmology (1960), Vol.126(9), pp.1301-1307
DOI: 10.1001/archopht.126.9.1301
PMID: 18779497
NLM abbreviation: Arch Ophthalmol
ISSN: 0003-9950
eISSN: 1538-3601
Publisher: American Medical Association; United States
Grant note: Howard Hughes Medical Institute
Language: English
Date published: 09/2008
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; 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: 9983979985702771

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