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Purpose:Congenital achromatopsia or rod monochromatism is a rare autosomal recessive condition defined by a severe loss of cone photoreceptor function in which rods purportedly retain normal or near-to-normal function. This report describes the results of electroretinography in two siblings withCNGB3-associated achromatopsia. Methods:Full field light- and dark-adapted electroretinograms (ERGs) were recorded using standard protocols detailed by the International Society for Clinical Electrophysiology of Vision (ISCEV). We also examined rod-mediated ERGs using series of stimuli that varied over a 6 log unit range of retinal illuminances (−1.9–3.5 log scotopic trolands). Results:Dark-adapted ERGs in achromatopsia patients exhibited severely reduced b-wave amplitudes with abnormalb:aratios (1.3 and 0.6). In comparison, the reduction in a-wave amplitude was less marked. The rod-mediated ERG took on an electronegative appearance at high-stimulus illuminances. Conclusion:Although the defect that causes achromatopsia is primarily in the cone photoreceptors, our results reveal an accompanying disruption of rod function that is more severe than has previously been reported. The differential effects on the b-wave relative to the a-wave points to an inner-retinal locus for the disruption of rod function in these patients. [ABSTRACT FROM PUBLISHER]

Background : Bornholm eye disease (BED) is a rare X-linked cone dysfunction disorder with high myopia, amblyopia, and color vision defects. Materials and methods: Visual and ocular outcomes in a family where two of five siblings had molecularly confirmed BED are reported. Ophthalmological assessments included best-corrected visual acuity (BCVA), color vision test, and optical coherence tomography (OCT). Medical records, electroretinography (ERG), and genetic analyses were re-evaluated. Results: Two male siblings had confirmed BED with myopia and protanopia. The younger brother had high myopia, subnormal BCVA, and ocular fundi that showed tilted discs, crescent shaped peripapillary atrophy, and visible choroidal vessels. OCT confirmed retinal and choroidal atrophy. The older brother was lightly myopic with normal/subnormal BCVA and subtle findings in the fundi. Both brothers had abnormal ERG recordings with a decreased cone response. They also had a structurally intact OPN1LW/OPN1MW gene cluster. The OPN1LW gene was shown to carry a deleterious variant combination in exon 3 known to result in mis-splicing of opsin mRNA and acknowledged as LIAVA amino acid delineation (Leu153-Ile171-Ala174-Val178-Ala180), while the OPN1MW gene exon 3 showed a non-pathogenic variant combination (MVVVA). Another normal-sighted brother carried another wildtype variant combination (LVAIS) in exon 3 of the OPN1LW gene. Conclusions: The two affected brothers demonstrated a large variability in their phenotypes even though the genotypes were identical. They presented a disease-associated haplotype in exon 3 of OPN1LW that has been described as the molecular cause of BED.

Purpose: To report a case of a 9-year-old child with neurofibromatosis type 1 (NF1) and Jalili syndrome, the latter denoting a rare combination of cone-rod dystrophy and amelogenesis imperfecta., Methods: Detailed ophthalmological and electrophysiological examinations were carried out and blood samples were taken from the patient and her father for molecular genetic analysis by direct DNA sequencing of the NF1 and the ancient conserved domain protein 4 (CNNM4) gene., Results: The diagnosis of neurofibromatosis type 1 (NF1) could be confirmed clinically and genetically. Furthermore, cone-rod dystrophy and amelogenesis imperfecta could be observed as typical features of a rare condition, acknowledged as Jalili syndrome. The diagnosis was assured on the basis of clinical examinations and molecular genetic analysis of the CNNM4 gene, which was previously shown to cause Jalili syndrome., Conclusion: Our case shows a unique combination of NF1 and Jalili syndrome. The random association of two diseases is unusual and deserves attention. This case highlights the importance not only of detailed clinical examination, but also of molecular genetic analysis, which together provide a precise diagnosis.

Background: Heterozygous mutations in GUCA1A (MIM # 600364) have been identified to cause autosomal dominantly inherited cone dystrophy, cone rod dystrophy and macular dystrophy. However, the role of GUCA1B gene mutations in inherited retinal disease has been controversial. We therefore performed a mutation analysis of the GUCA1B gene in a clinically well characterized group of patients of European and North-American geographical origin with autosomal dominantly inherited cone dystrophy and cone rod dystrophy., Material and Methods: Twenty-four unrelated patients diagnosed with cone dystrophy or cone rod dystrophy according to standard diagnostic criteria and a family history consistent with an autosomal dominant mode of inheritance were included in the study. Mutation analysis of all coding exons of the GUCA1B gene was performed by polymerase chain reaction amplification of genomic DNA and subsequent DNA sequencing., Results: Three different sequence variants, c.-17T>C, c.171T>C, c.465G>T were identified. The sequence variant c.465G>T encodes a conservative amino acid substitution, p.Glu155Asp, located in EF-hand 4, the calcium binding site of GCAP2 protein. All sequence variants were previously reported in healthy subjects., Conclusion: The absence of clearly pathogenic mutations in the selected patient group suggests that the GUCA1B gene is a minor cause for retinal degenerations in Europeans or North-Americans.

The first mutation in PITPNM3, a human homologue of the Drosophila retinal degeneration (rdgB not not) gene was reported in two large Swedish families with autosomal dominant cone dystrophy. To establish the global impact that PITPNM3 has on retinal degenerations we screened 163 patients from Denmark, Germany, the UK, and USA. Four sequence variants, two missence mutations and two intronic changes were identified in the screen. Thus, mutations in PITPNM3 do not appear to be a major cause of cone or cone-rod dystrophy.

Purpose: To describe the clinical phenotype, with emphasis on the electrophysiological findings, of patients with autosomal recessive rod monochromacy (RM) and defined mutations in the CNGA3/CNGB3 genes., Methods: RM patients from eight different families were included in the study. Their genotypes were determined by DNA sequencing and/or RFLP analysis of PCR-amplified genomic segments of the CNGA3 and CNGB3 genes. For comparison, we investigated one patient with blue-cone monochromacy (BCM). The clinical examination included best-corrected visual acuity, fundus examination, and full-field ERG. In six patients, the examination was complemented by multifocal ERG (MERG)., Results: Three patients had three different CNG3A genotypes. Five patients were homozygous and one patient compound heterozygous for a 1-bp deletion (1148delC) in the CNGB3 gene. All patients examined presented with a visual acuity of 0.1-0.15. Small residual cone responses were noted in four young RM patients. The oldest patient examined (age 47 years) presented with pigmentary changes in the mid-peripheral retina and concentric constrictions of the visual fields., Conclusions: Patients with RM and mutations in the CNGA3/CNGB3 genes presented a similar clinical phenotype, confirming the essential function of both the alpha- and beta-subunits of the cGMP-gated cation channel in cone photoreceptor function. Small remaining cone responses in a few of the younger patients and mid-peripheral pigmentary degenerations in the oldest patient examined indicate that there could be some degree of progression in retinal dysfunction in at least some patients with RM.