X-linked retinitis pigmentosa associated with a 2-base pair insertion in codon 99 of the RP3 gene RPGR

R G Weleber; N S Butler; W H Murphey; V C Sheffield; E M Stone

doi:10.1001/archopht.1997.01100160599013

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X-linked retinitis pigmentosa associated with a 2-base pair insertion in codon 99 of the RP3 gene RPGR

Journal article

Peer reviewed

X-linked retinitis pigmentosa associated with a 2-base pair insertion in codon 99 of the RP3 gene RPGR

R G Weleber, N S Butler, W H Murphey, V C Sheffield and E M Stone

Archives of ophthalmology (1960), Vol.115(11), pp.1429-1435

11/1997

DOI: 10.1001/archopht.1997.01100160599013

PMID: 9366675

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Abstract

Mutations in the RPGR gene at the RP3 locus have been found to cause x-linked retinitis pigmentosa in some families. To identify a previously undescribed 2-base pair insertion in codon 99 of the RPGR gene and to describe the phenotype in a well-characterized family with X-linked retinitis pigmentosa. Case reports with clinical features, fluorescein angiography, kinetic perimetry, electrophysiological studies, and molecular genetics. University medical centers. Eight members of the family were screened for the codon 99 insertion in the RPGR gene. Three affected males were found to be hemizygous for the 2-base pair insertion; 2 carriers were heterozygous. This insertion creates a frameshift that would be expected to cause a premature arrest of translation after only 132 amino acids (683 amino acids less than the normal protein). The affected males had typical retinitis pigmentosa with visual field contraction and abnormal findings on electroretinograms with little to no rod activity, profoundly subnormal residual cone responses to single flash and 30-Hz flicker stimuli, and prolonged b-wave implicit times. The electroretinogram of a 49-year-old carrier showed amplitudes that were roughly half of normal. Carrier women did not show a tapetallike fundus reflex but showed asymmetrical patchy pigmentary disturbances consistent with lyonization. A frameshifting 2-base pair insertion at codon 99 of the RPGR gene produced typical retinitis pigmentosa and carrier findings (but no tapetallike reflex) in this family.

Frameshift Mutation

Humans

Middle Aged

Male

DNA Primers - chemistry

Polymorphism, Single-Stranded Conformational

DNA Mutational Analysis

Visual Fields

DNA Transposable Elements - genetics

Adult

Female

Codon - genetics

Genetic Linkage - genetics

Retinitis Pigmentosa - physiopathology

X Chromosome - genetics

Fluorescein Angiography

Electroretinography

Retina - physiopathology

Retinitis Pigmentosa - genetics

Visual Acuity

Proteins - genetics

Carrier Proteins - genetics

Pedigree

Adolescent

Mutagenesis, Insertional

Visual Field Tests

Eye Proteins

Retina - pathology

Retinitis Pigmentosa - pathology

Details

Title: Subtitle: X-linked retinitis pigmentosa associated with a 2-base pair insertion in codon 99 of the RP3 gene RPGR
Creators: R G Weleber - Department of Ophthalmology, Oregon Health Sciences University, Portland, USA. weleberr@ohsu.edu
N S Butler
W H Murphey
V C Sheffield
E M Stone
Resource Type: Journal article
Publication Details: Archives of ophthalmology (1960), Vol.115(11), pp.1429-1435
DOI: 10.1001/archopht.1997.01100160599013
PMID: 9366675
NLM abbreviation: Arch Ophthalmol
ISSN: 0003-9950
eISSN: 1538-3601
Publisher: American Medical Association; United States
Grant note: EY10539 / NEI NIH HHS
Language: English
Date published: 11/1997
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983980005702771

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