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
Department of Ophthalmology, Oregon Health Sciences University, Portland, USA. weleberr@ohsu.edu
BACKGROUND: Mutations in the RPGR gene at the RP3 locus have been found to
cause x-linked retinitis pigmentosa in some families. OBJECTIVES: 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. DESIGN: Case reports with clinical features,
fluorescein angiography, kinetic perimetry, electrophysiological studies,
and molecular genetics. SETTING: University medical centers. PATIENTS:
Eight members of the family were screened for the codon 99 insertion in the
RPGR gene. RESULTS: 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. CONCLUSION: 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.
