Severe bilateral necrotising retinitis caused by Toxoplasma gondii in a patient with systemic lupus erythematosus and diabetes mellitus (original) (raw)
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Genomics, 1998
A). Other RIEG cases have subsequently been reported The autosomal dominant disorder Rieger syndrome to be associated with similar cytogenetic changes (1, (RIEG) shows genetic heterogeneity and has a pheno- 10, 18, 28,. The DNA markers with high lod type characterized by malformations of the anterior scores in RIEG families were then mapped with respect segment of the eye, failure of the periumbilical skin to to breakpoints of balanced translocations segregating involute, and dental hypoplasia. The main locus for with RIEG (3, 9,. From one such study, a bicoid-RIEG was mapped to the 4q25-q27 chromosomal segrelated homeobox transcription factor gene called ment using a series of cytogenetic abnormalities as RIEG has recently been cloned (25). The involvement well as by genetic linkage to DNA markers. Recently, of this gene in the pathogenesis of RIEG was proven a bicoid-related homeobox transcription factor gene using multiple lines of evidence: mutations that segrecalled RIEG has been cloned, characterized, and gated with the disorder, as well as de novo mutations proven to cause the 4q25 linked RIEG. Its mode of acin unrelated RIEG families, were identified, and the tion in the pathogenesis of RIEG was not conclusively mouse analogue (Rieg) mRNA was found to be highly proven, since most etiological mutations detected in expressed in the eye mesenchyme, maxillary and manthe RIEG sequence caused amino acid substitutions dibular epithelia, and umbilical cord, consistent with or splice changes in the homeodomain. Through FISH the affected sites in the human disorder.
Phenotypic Variability and Asymmetry of Rieger Syndrome Associated with PITX2 Mutations
Investigative Ophthalmology Amp Visual Science, 2000
Rieger syndrome is an autosomal dominant condition characterized by a variable combination of anterior segment dysgenesis, dental anomalies, and umbilical hernia. To date, reports have shown mutations within the PITX2 gene associated with Rieger syndrome, iridogoniodysgenesis, and iris hypoplasia. The purposes of this study were to determine the range of expression and intrafamilial variability of PITX2 mutations in patients with anterior segment dysgenesis.
Journal of Medical Genetics, 1997
Rieger syndrome (RS) is an autosomal dominant disorder of morphogenesis characterised by malformation of the anterior segment of the eye, dental hypoplasia, and failure of the periumbilical skin to involute. RS has been mapped to the 4q25-q27 chromosomal segment by a series of cytogenetic studies as well as by genetic linkage to DNA markers. It was first localised to chromosome 4q based on an association with a constitutional deletion of 4q23-q27. In this paper we localise the proximal breakpoint of this deletion from the original patient, and we describe a new family with a de novo balanced reciprocal translocation t(4;12)(q25;qlS) segregating with full RS in two generations. Using FISH and the P1 artificial chromosomes (PACs) as probes, we have physically localised both the deletion and the translocation breakpoints between genetic markers which are known to be strongly linked to RS. We have mapped both the proximal deletion breakpoint and the translocation breakpoint within a region between two groups of PACs bearing the markers D4S2945 (on the centromeric side) and D4S193 and D4S2940 (on the telomeric side). We believe that these recombinant bacterial clones derived directly from genomic DNA (not subcloned from YACs) will be valuable complementary tools in the efforts to clone the RS gene and to construct a full transcriptional and sequence ready map of this region.
Corneal deposits after the topical use of ofloxacin in two children with vernal keratoconjunctivitis
British Journal of Ophthalmology, 2003
Aniridia-associated cytogenetic rearrangements suggest that a position effect may cause the mutant phenotype. Hum Mol Genet 1995;4:415-22. 3 Nishimura DY, Swiderski RE, Alward WL, et al. The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25. Nat Genet 1998;19:140-7. 4 Flomen RH, Vatcheva R, Gorman PA, et al. Construction and analysis of a sequence-ready map in 4q25: Rieger syndrome can be caused by haploinsufficiency of RIEG, but also by chromosome breaks approximately 90 kb upstream of this gene. Genomics 1998;47:409-13. 5 Gardner RJM, Sutherland GR. Chromosome abnormalities and genetic counselling.
Investigative Ophthalmology & Visual Science, 2017
Retinitis pigmentosa (RP) causes progressive photoreceptor loss resulting from mutations in over 80 genes. This study identified the genetic cause of RP in three members of a non-consanguineous pedigree. Detailed ophthalmic evaluation was performed in the three affected family members. Whole exome sequencing (WES) and whole genome sequencing (WGS) were performed in the three affected and the two unaffected family members and variants were filtered to detect rare, potentially deleterious variants segregating with disease. WES and WGS did not identify potentially pathogenic variants shared by all three affected members. However, WES identified a previously reported homozygous nonsense mutation in KIZ (c.226C>T, p.Arg76*) in two affected sisters, but not in their affected second cousin. WGS revealed a novel 1.135 kb homozygous deletion in a retina transcript of C21orf2 and a novel 30.651 kb heterozygous deletion in CACNA2D4 in the affected second cousin. The sisters with the KIZ mutation carried no copies of the C21orf2 or CACNA2D4 deletions, while the second cousin with the C21orf2 and CACNA2D4 deletions carried no copies of the KIZ mutation. This study identified two independent, homozygous mutations in genes previously reported in autosomal recessive RP in a non-consanguineous family, and demonstrated the value of WGS when WES fails to identify likely disease-causing mutations.
Genes, 2017
Retinitis pigmentosa (RP) causes progressive photoreceptor loss resulting from mutations in over 80 genes. This study identified the genetic cause of RP in three members of a non-consanguineous pedigree. Detailed ophthalmic evaluation was performed in the three affected family members. Whole exome sequencing (WES) and whole genome sequencing (WGS) were performed in the three affected and the two unaffected family members and variants were filtered to detect rare, potentially deleterious variants segregating with disease. WES and WGS did not identify potentially pathogenic variants shared by all three affected members. However, WES identified a previously reported homozygous nonsense mutation in KIZ (c.226C>T, p.Arg76*) in two affected sisters, but not in their affected second cousin. WGS revealed a novel 1.135 kb homozygous deletion in a retina transcript of C21orf2 and a novel 30.651 kb heterozygous deletion in CACNA2D4 in the affected second cousin. The sisters with the KIZ mutation carried no copies of the C21orf2 or CACNA2D4 deletions, while the second cousin with the C21orf2 and CACNA2D4 deletions carried no copies of the KIZ mutation. This study identified two independent, homozygous mutations in genes previously reported in autosomal recessive RP in a non-consanguineous family, and demonstrated the value of WGS when WES fails to identify likely disease-causing mutations.
Nature genetics, 1998
A number of different eye disorders with the presence of early-onset glaucoma as a component of the phenotype have been mapped to human chromosome 6p25. These disorders have been postulated to be either allelic to each other or associated with a cluster of tightly linked genes. We have identified two primary congenital glaucoma (PCG) patients with chromosomal anomalies involving 6p25. In order to identify a gene involved in PCG, the chromosomal breakpoints in a patient with a balanced translocation between 6p25 and 13q22 were cloned. Cloning of the 6p25 breakpoint led to the identification of two candidate genes based on proximity to the breakpoint. One of these, FKHL7, encoding a forkhead transcription factor, is in close proximity to the breakpoint in the balanced translocation patient and is deleted in a second PCG patient with partial 6p monosomy. Furthermore, FKHL7 was found to harbour mutations in patients diagnosed with Rieger anomaly (RA), Axenfeld anomaly (AA) and iris hypo...