Biomedical subjects

John D Mollon

Publications and source records attributed to John D Mollon.

4 recordsLinked to original sources

PubMed2005

X-linked cone dysfunction syndrome with myopia and protanopia.

PURPOSE: To perform a detailed clinical, psychophysical, and molecular assessment of members of 4 families with an unusual X-linked cone dysfunction syndrome associated with myopia. PARTICIPANTS: Affected and unaffected members of 4 British nonconsanguineous families. METHODS: Subjects underwent both detailed clinical examination and psychophysical testing. After informed consent was obtained, blood samples were taken for DNA extraction, and molecular genetic analysis was performed. The strategy for molecular analysis was to amplify the coding regions of the long and middle wavelength-sensitive cone opsin genes and the upstream locus control region by polymerase chain reaction and to examine these fragments for mutations by sequencing of DNA. RESULTS: The phenotype was almost identical in all 4 families, consisting of moderate to high myopia, astigmatism, moderately reduced acuity, and normal fundi. Electroretinography showed abnormal cone but normal rod responses. Psychophysical testing showed a selective impairment of long cones in combination with well-preserved middle cone and short cone function. There was no evidence to suggest that the phenotype was progressive. Molecular analysis of the X-linked opsin gene array in the 4 families indicated that affected males have inherited the same X-chromosome from their mother. In 2 families, a long/middle hybrid gene was detected. In a third family, the commonly described deleterious Cys203Arg amino acid substitution was identified in both the long and middle opsin genes. In the fourth family, the only abnormality was absence of a middle opsin exon 2; the cause of the protanopia in this family is uncertain. CONCLUSIONS: The X-linked cone dysfunction syndrome associated with myopia and dichromacy described here has many similarities to Bornholm eye disease, a condition previously mapped to Xq28. Except for the Cys203Arg substitution in one family, no alterations in the opsin gene array were identified that could underlie the cone dysfunction. It is therefore possible that the cone dysfunction may have a genetic origin different from that of the dichromacy.

Adolescent↗

PubMed2004

Progressive cone dystrophy associated with mutation in CNGB3.

PURPOSE: To determine the molecular basis for phenotypic variability in a three-generation consanguineous family containing a single individual with complete achromatopsia and three individuals with progressive cone dystrophy. METHODS: Four affected individuals underwent ophthalmic examination, electrophysiological assessment, color fundus photography, and psychophysical testing. Blood samples were obtained for DNA extraction and mutation screening of the cone-specific cGMP-gated (CNG) channel protein gene CNGB3 was undertaken. RESULTS: The clinical findings in one family member were consistent with a diagnosis of complete achromatopsia, with nystagmus, photophobia, and poor visual acuity from early infancy and complete color-blindness, normal fundi, and absent cone responses with normal rod responses on electroretinography (ERG). Mutation analysis revealed her to be homozygous for the common CNGB3 achromatopsia mutation, 1148delC (Thr383fs). In contrast, the three other symptomatic individuals in the family had findings consistent with progressive cone dystrophy. Their visual problems began later in childhood (ranging from 3 to 14 years of age) and there was evidence of progressive deterioration in cone function. All three had a marked tritanopic color vision defect and fundoscopy revealed bilateral macular atrophy. Electrophysiological testing of these three subjects demonstrated clear evidence of progressive deterioration of cone responses over time; rod responses were normal. All three individuals with this progressive phenotype were found to be compound heterozygotes for the 1148delC (Thr383fs) frameshift mutation and a novel Arg403Gln missense mutation in CNGB3. CONCLUSIONS: Mutations in CNGB3, which have been shown to cause achromatopsia, are now shown to be associated with autosomal recessive progressive cone dystrophy. In this study, a novel Arg403Gln mutation was identified, located in the middle of the pore domain of the cone CNG cation channel beta-subunit, which when associated with the nonsense mutation Thr383fs, resulted in progressive cone dystrophy.

Adult↗

PubMed2003

Comparison at a distance.

The visual system is known to contain hard-wired mechanisms that compare the values of a given stimulus attribute at adjacent positions in the visual field; but how are comparisons performed when the stimuli are not adjacent? We ask empirically how well a human observer can compare two stimuli that are separated in the visual field. For the stimulus attributes of spatial frequency, contrast, and orientation, we have measured discrimination thresholds as a function of the spatial separation of the discriminanda. The three attributes were studied in separate experiments, but in all cases the target stimuli were briefly presented Gabor patches. The Gabor patches lay on an imaginary circle, which was centred on the fixation point and had a radius of 5 deg of visual angle. Our psychophysical procedures were designed to ensure that the subject actively compared the two stimuli on each presentation, rather than referring just one stimulus to a stored template or criterion. For the cases of spatial frequency and contrast, there was no systematic effect of spatial separation up to 10 deg. We conclude that the subject's judgment does not depend on discontinuity detectors in the early visual system but on more central codes that represent the two stimuli individually. In the case of orientation discrimination, two naive subjects performed as in the cases of spatial frequency and contrast; but two highly trained subjects showed a systematic increase of threshold with spatial separation, suggesting that they were exploiting a distal mechanism designed to detect the parallelism or non-parallelism of contours.

Contrast Sensitivity↗

PubMed2002

Conditions under which stereopsis and motion perception are blind.

We describe modified random-dot stereograms in which the corresponding elements differ from non-corresponding elements in colour, size, and luminance. Despite these visible differences between the elements, depth perception collapses when the spatially integrated luminous flux is similar for the corresponding and non-corresponding elements. Our results suggest that a low-pass spatial filter precedes the mechanism that recognises disparity. A similar phenomenon is observed for the perception of coherent motion in random-dot kinematograms. Our modified stereograms and kinematograms may find other uses when experimenters wish to study the contribution of colour to visual processes and require a method of eliminating edge artifacts.

Adult↗