RPGR ORF15 genotype and clinical variability of retinal degeneration in an Australian population.

BACKGROUND: Mutations in the retinitis pigmentosa GTPase regulator gene (RPGR) are estimated to cause up to 20% of all Caucasian retinitis pigmentosa and up to 75% of cases of X-Linked RP (XLRP). Exon open reading frame 15 (ORF15) is a purine-rich mutation hotspot. Mutations in RPGR ORF15 have also been documented to cause X linked cone-rod dystrophy (XLCORD) and atrophic macular degeneration at an unknown frequency. METHODS: From a hospital clinic population, probands with probable XLRP and XLCORD were screened for RPGR ORF15 mutations and fully phenotyped. RESULTS: Four different RPGR ORF15 mutations were found in four probands. All mutations in the ORF15 exon resulted in premature truncation of the RPGR protein. Three were nonsense mutations: c.507G>T (p.E169stop), c.867G>T (p.G289stop), c.897G>T (p.E299stop) and the fourth a single nucleotide insertion c.1558-1559insA (p.S522fs 525stop). One family exhibited typical XLRP, two XLCORD and one a combination of the phenotypes. CONCLUSION: RPGR ORF15 mutations produce intrafamilial and interfamilial clinical variability with varying degrees of cone degeneration. In an Australian clinic population RPGR ORF15 mutations cause XLCORD in addition to XLRP.

Bedside tests of saccades after head injury.

OBJECTIVES: To compare the techniques of bedside and infrared oculographic tests of saccades and to compare the results of both tests in control subjects and in patients with traumatic brain injuries (TBI). MATERIALS AND METHODS: The authors elicited single memory-guided saccades, antisaccades, and self-paced saccades in 19 TBI subjects and 26 age-matched control subjects at the bedside. Taped instructions were used to ensure that the timing and sequence of each stimulus (index finger flexion) were the same in all subjects and as close as possible to those used in both the current and previous laboratory studies. RESULTS: Self-paced saccade rate was significantly decreased in patients with TBI. The increased error rate in single memory-guided saccades and antisaccades was not statistically significant. CONCLUSION: The authors concluded that the bedside saccade tests have limited value in patients with TBI because of the range of results and large overlap of the distributions of these two groups. The number of parameters that can be measured is limited. Bedside saccade tests are easier than infrared oculographic tests because the target remains visible.

Cerebral control of saccades and neuropsychological test results after head injury.

Abnormalities in the control of saccades have been described in patients with cerebral pathology.(1, 2) We assessed control of visually guided, reflexive and volitional saccades in 16 patients suffering severe traumatic brain injury and 12 controls and related the results to deficits on neuropsychological tests of speed of information processing and goal directed behaviour. All saccadic latencies were prolonged. Suppression of inappropriate saccades was impaired on volitional saccade tests which proved to be more sensitive in identifying impairment of goal directed behaviour than the neuropsychological test results. Patients' self-paced saccade rate was lower than controls' and correlated with performance on several visually mediated neuropsychological test results. Patients' visually guided, reflexive saccades were hypometric; this hypometria correlated with both visual and non-visual neuropsychological test results and with post-traumatic amnesia duration. Hypometria in reflexive saccades may reflect diffuse brain injury. Re-examination after 12 months revealed that the control of volitional saccades improved but there was no improvement in the visually guided reflexive saccade measures. The volitional saccade tests may be useful in documenting both impairment and subsequent recovery.

A new codon 15 rhodopsin gene mutation in autosomal dominant retinitis pigmentosa is associated with sectorial disease.

OBJECTIVE: To ascertain and characterize rhodopsin gene mutations in autosomal dominant retinitis pigmentosa and to correlate these mutations with the clinical phenotypes. METHODS: DNA was extracted from leukocytes, and the rhodopsin gene was amplified and analyzed using molecular-biological methods. Clinical and electrophysiological data were collected from patient charts. RESULTS: We found a disease-causing mutation that was previously undescribed, to our knowledge, for autosomal dominant retinitis pigmentosa within codon 15 of exon 1 of the rhodopsin gene. It was a single base-pair transversion (AAT to AGT) leading to a serine-for-asparagine substitution. This altered a glycosylation site in the intradiscal portion of the rhodopsin molecule. The pedigree examined demonstrated an inferior distribution of retinal pigmentary changes and predominantly superior visual field loss with relative preservation of electroretinographic amplitudes and good vision, which is consistent with sectorial or sectorial-like retinitis pigmentosa. CONCLUSIONS: A codon 15 rhodopsin gene mutation caused retinitis pigmentosa in the pedigree studied. There may be an association between intradiscal rhodopsin gene mutations and sectorial forms of retinitis pigmentosa.