Showing papers in "Ophthalmic Genetics in 2010"
TL;DR: Mutations in the FZD4 gene in this group of premature infants supports a role for the FzD4 pathway in the development of severe ROP and accounts for approximately 3% ofsevere ROP in Caucasian premature infants.
Abstract: Purpose: To determine whether mutations in the FZD4 gene are a risk factor for developing severe ROP.Methods: Three Canadian tertiary care centers recruited premature infants prospectively and retrospectively, and assigned affectation status based on the maximum degree of severity of ROP recorded in both eyes. Mutation screening of the FZD4 gene was performed using direct sequencing. All sequence changes were evaluated for functional significance.Results: Two novel FZD4 mutations (Ala370Gly or Lys203Asn) were identified in two infants from the severe ROP group (n=71). No mutation was detected in the mild to no ROP group (n=33), and the two novel mutations were absent in 173 random Caucasian samples. Mutation Ala370Gly was also found in one sibling and one parent of the affected infant, but no signs of familial exudative vitreoretinopathy (FEVR), a condition with phenotypic overlap with ROP known to be caused by FZD4 mutations, were present in either family member.Conclusions: Mutations in the FZD4 gene in...
47 citations
TL;DR: The optical coherence tomography and fundus autofluorescence measurements in patients with retinitis punctata albescens patients often show similar fundus changes but manifest a severe and progressive hereditary retinal dystrophy.
Abstract: Purpose: Fundus albipunctatus is a form of congenital stationary night blindness characterized by an early onset and nonprogressive impairment of night vision and the presence of numerous dull-white punctate lesions scattered throughout the fundus, while retinitis punctata albescens patients often show similar fundus changes but manifest a severe and progressive hereditary retinal dystrophy.Conclusions: In this study, we report the optical coherence tomography and fundus autofluorescence measurements in patients with these hereditary night blinding diseases.
43 citations
TL;DR: Clinical follow-up of ten young XLRS patients with a typical congenital retinoschisis phenotype revealed no significant decline in retinal function during this time period and the XLRS disease was relatively stable during this period of observation.
Abstract: Purpose: To investigate the retinal structure and function during the progression of X-linked retinoschisis (XLRS) from childhood to adulthood.Methods: Ten patients clinically diagnosed with XLRS were investigated at 6–15 years of age (mean age 9 years) with a follow-up 8 to 14 years later (mean 12 years). The patients underwent regular ophthalmic examination as well as testing of best corrected visual acuity (BCVA), visual field (VF) and assessment of full-field electroretinography (ERG) during their first visit. During the follow-up, the same clinical protocols were repeated. In addition, macular structure and function was examined with multifocal electroretinography (mfERG) and optical coherence tomography (OCT). The patients were 18–25 years of age (mean age 21 years) at the follow-up examination. All exons and exon-intron boundaries of RS1-gene were sequenced for gene mutations in 9 out of the 10 patients.Results: Best corrected VA and VF were stable during this follow-up period. No significant progr...
43 citations
TL;DR: This work shows a consanguineous family that carries a novel homozygous splice mutation IVS4-1G>A/IVS 4-1 G>A in ADAMTSL4 responsible for isolated autosomal recessive EL, thus confirming the involvement of this gene in this condition and underlining the major role of ADAMts proteases in zonular fibers homeostasis.
Abstract: Ectopia lentis (EL) is a zonular disease where alteration of the zonular fibers leads progressively to lens dislocation. It is most often associated with systemic diseases such as Marfan syndrome, Weill-Marchesani syndrome or homocystinuria. Isolated non syndromic ectopia lentis (IEL) is reported in families with autosomal inheritance, with dominant forms being more common than recessive. LTBP2 truncating mutations have been described as a cause of autosomal recessive ectopia lentis as a primary or secondary feature in patients showing ocular (eg, glaucoma) or extraocular manifestations (eg, Marfanoid habitus). Recently, ADAMTSL4 has been shown to be responsible for isolated autosomal recessive ectopia lentis in an inbred family. Herein we show a consanguineous family that carries a novel homozygous splice mutation IVS4-1G>A/IVS4-1G>A in ADAMTSL4 responsible for isolated autosomal recessive EL, thus confirming the involvement of this gene in this condition and underlining the major role of ADAMTS proteases in zonular fibers homeostasis.
31 citations
TL;DR: The results indicate an important role of OPA1 in mitochondrial dependent Ca2+ homeostasis and cell survival in RGCs, suggesting a possible patho-physiological mechanism involved in inherited optic neuropathies.
Abstract: Purpose: The regulation of Ca2+ entry and removal is a fine-tuned process which remains not well understood in mouse retinal ganglion cells (RGCs). The latter are known to be sensitive to dysfunctions of mitochondria, organelles playing a pivotal role in Ca2+ reuptake.Methods: We first described the Ca2+ signals of RGCs in response to varied drugs with Fura-2 imaging, and secondly tested the role of optic atrophy 1 or OPA1, the gene responsible for Autosomal Dominant Optic Atrophy, on mitochondrial ability to capture intracellular Ca2+ in cells transfected with the OPA1 small interfering ribonucleic acids (siRNAs).Results: In control RGCs, K+-evoked [Ca2+]i increase was blocked by the Ca2+ channel antagonists (Ni2++ Cd2+) and GABAA receptor agonist muscimol-induced [Ca2+]i responses were attenuated by the GABAA receptor antagonists, picrotoxin and gabazine. We also prove the presence of NMDA and AMPA/Kainate (glutamate receptor agonists) responsive receptors in this model. Application of cyclopiazonic aci...
30 citations
TL;DR: The phenotype associated with changes in the ZEB1 gene exhibits variable expression and incomplete penetrance and seems to have a low risk for secondary glaucoma or the need for keratoplasty compared to PPCD linked to 20p11.2.
Abstract: Purpose: To describe the ocular features of 6 Czech and British patients with posterior polymorphous corneal dystrophy (PPCD) caused by mutations in the zinc finger E-box binding homeobox 1 gene (ZEB1).Methods: Case note review of 4 individuals with p.E776fs mutation, one with p.Y719X and one with p.F375fs mutation within the ZEB1 gene.Results: Five individuals exhibited endothelial and Descemet membrane changes consistent with the diagnosis of PPCD. We concluded that one 70-year-old female who had a normal endothelium at both slit lamp and non-contact specular microscopy was a case of non-penetrance. The onset of disease was as early as 3 months after birth. One patient had irregular astigmatism with inferior corneal steepening on videokeratography, but without corneal thinning or other signs of keratoconus. Two others had corneal steepening >49D but with regular astigmatism. Three individuals underwent penetrating keratoplasty (PK) in 1 eye, with one patient treated for secondary glaucoma prior to the P...
29 citations
TL;DR: A difference is shown in the association of variations in ALR2, iNOS and TNFB genes with DR, when compared to previous reports; this could be attributed to differences between the study populations of the past and present report.
Abstract: Purpose: We previously reported the association of the Z-2 allele of the promoter dinucleotide repeat in the Aldose reductase (ALR2) gene, the (CCTTT)15 allele in the promoter of inductible nitric oxide synthase (iNOS) gene, and the (GT)13 promoter polymorphism in the tumor necrosis factor β (TNFB) gene with an increased risk for diabetic retinopathy (DR), and the Gly82Ser polymorphism in the receptor for advanced glycation end products (RAGE) gene and the (GT)9 allele of the TNFB gene with low-risk for DR in a hospital-based self-reported type 2 diabetes mellitus (T2DM) patients. We have repeated the study in a population-based south Indian cohort to validate the same variations in these genes.Materials and Methods: Type 2 diabetic patients with and without retinopathy (DR+ and DR− respectively) were recruited. (CA)n repeat, Gly82Ser, (CCTTT)n repeat and (GT)n repeat in ALR2, RAGE, iNOS and TNFB genes respectively were genotyped and their frequencies were analyzed using the relevant statistical tests.Res...
26 citations
TL;DR: Recessive p.R56W CRYAB mutation shows variable expressivity for lens opacity and may be an environmental risk factor for significant retinal degeneration in patients homozygous for the mutation.
Abstract: Purpose: To describe later retinal degeneration following childhood cataract surgery without intraocular lens implantation in a consanguineous family with developmental cataract from homozygous p.R56W mutation in CRYAB, a gene that encodes a heat-shock protein (αB-crystallin) in both retina and the lens.Methods: Prospective ophthalmologic examination and venous blood sampling for diagnostic CRYAB sequencing in the 12 available family members (7 siblings and their 2 parents, the siblings’ maternal aunt and her son, and the siblings’ maternal grandmother).Results: Those who underwent childhood cataract surgery (2 siblings, their mother, their maternal aunt) or who had visually-insignificant lens opacities (2 siblings, their maternal grandmother) were homozygous for p.R56W CRYAB mutation. Among these 7 affected family members, clinically-obvious rod-cone degeneration was present only in the only 2 adults who were aphakic since childhood from cataract surgery.Conclusions: Recessive p.R56W CRYAB mutation shows...
26 citations
TL;DR: eNOS gene variation may be a factor in the genetic propensity to T1DM and diabetic retinopathy that may have a prognostic value or may suggest interventional approaches to regulate eNOS in patients with diabetes.
Abstract: Purpose: Nitric oxide (NO) is a major mediator in vascular biology, regulating blood pressure and regional blood flow. NO and the enzymes required for its production may contribute to the aetiology of vascular pathologies. In diabetes, over-production of NO might play a role in the development of diabetic nephropathy, while reduced NO production may be related to the development of diabetic retinopathy and neuropathy, where VEGF (vascular endothelial growth factor) levels are increased in a counter regulatory manner. Among the three nitric oxide synthase (NOS) enzymes most attention has focussed on endothelial NOS (eNOS) because of its relevance to angiopathies.Methods: In this study the influence of a single nucleotide polymorphism at position -786 in the eNOS gene, where there is a C/T base substitution, on development of type 1 diabetes mellitus (T1DM) and its microvascular complications was studied in 249 British Caucasian type 1 diabetics using a case-control association design. Genotyping was carrie...
26 citations
TL;DR: In this paper, the association of genotypes with retinopathy of prematurity (ROP) was studied by microplate-Restriction Fragment Length Polymorphism Polymerase Chain Reaction (RFLP PCR).
Abstract: Purpose: Retinopathy of Prematurity (ROP) is a vasoproliferative disorder affecting preterm infants leading to visual impairment. ROP is more common in Caucasians than African Americans. Very low birth weight infants have immature retinas and are susceptible to ROP. Because of differences in individual responses to the treatment, various genetic factors have been looked into to understand the etiology of ROP. Endothelial nitric oxide (eNO) serves as a vasodilator, relaxes smooth muscle, prevents platelet aggregation, and facilitates improved blood flow and vascular tonicity. Mutant eNO synthase (eNOS) genotypes result in reduced nitric oxide levels by decreasing enzyme activity. Since eNO affects vasculature and ROP is a vascular disease, the present investigation was aimed at studying the association of genotypes with ROP.Methods: Two eNOS gene single nucleotide polymorphisms (SNPs) (T-786C, and G894T) were studied by microplate-Restriction Fragment Length Polymorphism Polymerase Chain Reaction (RFLP PCR...
24 citations
TL;DR: The mechanism and clinical progression appear to differ from that of idiopathic macular holes and, is likely related to an abnormality in Type IV collagen in basement membrane of retinal Muller cells.
Abstract: Purpose: To describe the evolution of a giant macular hole in a patient with Alport syndrome and review the literature.Methods: An observational case report is presented with serial clinical examination, visual acuity, fundus photographs, and ocular coherence tomography performed.Results: A man with Alport syndrome and a giant macular hole in one eye developed multiple, small lamellar macular holes which coalesced into a giant full thickness macular hole in the contralateral eye.Conclusions: Giant macular holes may occur in Alport syndrome. The mechanism and clinical progression appear to differ from that of idiopathic macular holes and, is likely related to an abnormality in Type IV collagen in basement membrane of retinal Muller cells. Anomalous vitreoretinal adhesion may also play a role. Previous cases of giant macular holes in the literature may not have been properly associated with Alport syndrome.
TL;DR: It is shown for the first time that large intragenic deletions of FRMD7 can also cause this form of nystagmus.
Abstract: Objective: To identify the disease-causing mutation in a large 3 generation pedigree of X-linked congenital nystagmus. Methods: Twenty-three members of a single pedigree, including 7 affected males, 2 affected females, 5 obligate carriers, and 9 unaffected family members were tested for mutations in the FRMD7 gene using PCR-based DNA sequencing assays and multiplex PCR assays for deletions. Results: A hemizygous deletion of exons 2, 3, and 4 of FRMD7 was detected in all affected males in the family and was absent from 40 control subjects. Conclusions: A range of missense, nonsense, frameshift, and splicing mutations in FRMD7 have been shown to cause X-linked congenital nystagmus. Here we show for the first time that large intragenic deletions of FRMD7 can also cause this form of nystagmus.
TL;DR: The present report confirms the wide clinical spectrum of Peters plus syndrome, underlines the major clinical criteria of the syndrome and the major implication of B3GALTL gene in this condition, and improves dramatically genetic counselling for the families.
Abstract: Peters plus syndrome is an autosomal recessive rare congenital disorder defined by corneal Peters anomaly with short disproportionate stature, development delay and dysmorphic facial features. In addition, cardiac, genito-urinary and/or central nervous system malformations can be present. Mutations in the beta-1,3-galactosyltransferase-like glycosyltransferase gene (B3GALTL) have been reported in patients with Peters plus syndrome prompting phenotype-genotype studies because of the variable clinical spectrum related to the syndrome. A 20 month old boy presenting with bilateral Peters anomaly in association with multiple developmental anomalies including cerebral malformations was found to carry a novel homozygous B3GALTL nonsense mutation [p.Tyr366X]. This is the first stop mutation described in association with this gene. The present report confirms the wide clinical spectrum of Peters plus syndrome, underlines the major clinical criteria of the syndrome and the major implication of B3GALTL gene in this condition. Ophthalmologic examination in multiple developmental anomalies remains an important clinical issue that may lead to specific gene screening. In Peters plus syndrome B3GALTL molecular test provides diagnosis confirmation and improves dramatically genetic counselling for the families.
TL;DR: This 14 year old Saudi boy had clinical features similar to patients reported with the 6q terminal deletion syndrome, and had an unusual ocular motility pattern and thick corneas, features that may be more common than previously recognized.
Abstract: Purpose: To correlate the clinical phenotype with the genotype of a boy with a terminal deletion of chromosome 6q and to compare these observations to previous reports of 6q deletions and review of the literature.Methods: Careful clinical evaluation, conventional cytogenetic analysis on GTG-banded chromosomes and 244K array CGH analysis.Results: This 14 year old Saudi boy had modest mental retardation, seizures, microcephaly, cortical dysplasia, a non-comitant esotropia, impersistent eccentric gaze, congenital nystagmus, thick corneas, and substantial myopia. He had a de novo 10.79 Mb deletion on chromosome 6 from 6q25.3 to 6qter. The deleted region extended from nucleotide 159929512 to 170723629 and encompassed 87 genes. Eleven genes remained within the proband’s deleted region after excluding genes located in deleted areas reported in phenotypically normal individuals. Among those 11 genes, only the TBP (TATA box binding protein) gene has been associated with any symptom or sign observed in our patient....
TL;DR: Long term follow up with microperimetric testing could be useful in monitoring any progressive loss of retinal function in choroideremia carriers.
Abstract: Purpose: To evaluate structural retinal changes and macular function by a combined spectral domain optical coherence tomography/ scanning laser ophthalmoscope (OCT/ SLO) microperimetry device in choroideremia carriers.Methods and Materials: Ten choroideremia carriers were included in the study. All subjects had a complete ophthalmic examination in addition to Goldmann kinetic visual fields, OCT and microperimetry testing on a commercially available Spectral Domain (SD) OCT/SLO combination system.Results: Microperimetry results demonstrated focal areas of threshold abnormalities in 50% of the subjects. OCT findings show subtle retinal pigment epithelium (RPE) irregularities with attenuation more pronounced outside the macular region.Conclusions: Long term follow up with microperimetric testing could be useful in monitoring any progressive loss of retinal function in choroideremia carriers.
TL;DR: This is the first study to show that polymorphisms in anti-inflammatory cytokine genes are associated with susceptibility to Graves’ ophthalmopathy.
Abstract: Background: Various polymorphisms occur in cytokine genes involved in inflammatory processes in Graves’ ophthalmopathy (GO). Anti-inflammatory cytokines such as transforming growth factor- β (TGF-β), interleukin-10 (IL-10) and interleukin-4 (IL-4) are among those believed to be involved in the disease process. In this study, we investigated the association between 8 polymorphisms within the mentioned cytokines and GO.Methods: The following polymorphisms were studied in 50 patients with GO, 57 Graves’ patients without GO and 140 healthy individuals using polymerase chain reaction with sequence-specific primers: TGF-β (+869C/T, +915G/C), IL-10 (-1082A/G, -819C/T, -592C/A) and IL-4 (-1098T/G, -590T/C, -33C/T). A corrected p value less than 0.05 was considered statistically significant.Results: The TGF-β +915C allele (Odds Ratio [OR] = 2.20) and CC genotype (OR = 7.50) as well as +869C allele (OR = 2.21) showed significant correlations with GO. Regarding IL-4 polymorphisms, the -1098G allele (OR = 2.09) and G...
TL;DR: These are the studies by several investigators whose contributions illuminated the path to the current understanding of Stargardt disease and helped to advance progress toward future therapeutic trials for the unfortunate group of patients afflicted with this disease.
Abstract: The historical evolution in the understanding of Stargardt macular dystrophy (fundus flavimaculatus) from the initial description by Karl Stargardt, identification of mutations in the ABCA4 gene, to the development of a mouse model for the human disease, is described. Highlighted are the studies by several investigators whose contributions illuminated the path to our current understanding of Stargardt disease and helped to advance progress toward future therapeutic trials for the unfortunate group of patients afflicted with this disease.
TL;DR: The first histological investigation could not confirm the presence of abnormal elastin in the cornea, but another gene could be responsible, and a possible genetic link with keratoconus was considered.
Abstract: Purpose: To report two memorable clinical comorbid cases of Williams–Beuren syndrome (WBS) associated with keratoconus (KC). WBS is known to be an abnormal systemic development caused by a microdeletion of contiguous genes in chromosome 7q11.23, which includes the elastin gene. KC is currently suspected to have a genetic origin but the responsible gene has not been clearly identified.Methods: KC and WBS is described for two cases. Risk factors for KC were investigated by interviewing parents, and WBS was confirmed by fluorescence in-situ hybridization (FISH). Histological analysis with Orcein (coloring specific to elastin) on the receiver corneal button of patient 1 was carried out.Results: Because of the rarity of both pathologies and the absence of other risk factors for developing keratoconus, we considered a possible genetic link. The association had never been reported in the literature. The first histological investigation could not confirm the presence of abnormal elastin in the cornea, but another...
TL;DR: An X-autosome chromosomal translocation combined with non-random inactivation of the normal X-chromosome in a woman resulted in the phenotypic findings of choroideremia and ectodermal dysplasia.
Abstract: Background: Choroideremia is an X-linked recessive disorder characterized by vision loss with progressive atrophy of the retinal photoreceptors, retinal pigment epithelium (RPE), and choriocapillaris. Ectodermal dysplasia is a heterogeneous group of disorders characterized by a deficiency of two or more ectodermal derivatives. We report on the phenotypic and genetic characteristics of a 29-year-old woman with both choroideremia and ectodermal dysplasia.Materials and Methods: Observational case report with physical and ophthalmic examination, fluorescein angiography (FA), visual field testing, electroretinography, and cytogenetic analysis. This study adhered to the tenets of the Declaration of Helsinki and The New York Eye and Ear Infirmary Institutional Review Board guidelines.Results: Physical and ocular examination revealed hypotrichosis, hypohidrosis, full dentures, meibomian gland hypoplasia, and a decrease in corneal tear film. Visual acuity was hand motions in the right eye and 20/50 in the left eye...
TL;DR: The results suggest that a different set of LHON-causing mutations is present in the South Indian population than in the European population, and further study of subjects with LHON from India may lead to the discovery of novel disease-cause mutations and/or genes.
Abstract: AbstrA ct Background: Three mitochondrial mutations account for 95% of Leber’s hereditary optic neuropathy (LHON) in the European population: G3640A, G11778A and T14484C. The purpose of the study was to investigate the frequency of these mitochondrial DNA mutations in LHON patients from a South Indian population. Methods: LHON was diagnosed by inheritance pattern, ophthalmologic examination, and by exclusion of non-LHON forms of optic neuropathy. Ninety unrelated LHON patients and 20 at-risk family members (5 with LHON and 15 without LHON) underwent molecular screening for the mitochondrial DNA mutations G3640A, G11778A and T14484C by amplification refractory mutation system (ARMS) polymerase chain reaction (PCR). Positive results were confirmed with bi-directional sequencing. Results: The G11778A mutation was detected in 8 of 90 (8.9%) LHON families. The T14484 mutation was detected in 3 of 90 (3.3%) LHON families. No instances of the G3460A mutation were detected. Other variants were incidentally detected by the DNA sequencing assay. Conclusions: Three mitochondrial mutations (G3640A, G11778A and T14484C) account for the vast majority of LHON cases in Europe. However, these mutations were detected in only 11 (12%) of 90 LHON families from Southern India in our study. These results suggest that a different set of LHON-causing mutations is present in the South Indian population than in the European population. Further study of subjects with LHON from India may lead to the discovery of novel diseasecausing mutations and/or genes.
TL;DR: The D allele of the ACE gene is independently associated with diabetic retinopathy in Iranian type 2 diabetic patients.
Abstract: Background: The role of genetic factors in diabetic retinopathy (DR) is unclear. We investigated the relationship between DR and an insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE) gene in Iranian patients with type 2 diabetes without overt nephropathy.Methods: A total of 178 consecutive type 2 diabetic patients with DR (Group A) and 206 type 2 diabetic patients without DR (Group B) were studied. The following variables were determined: age, sex, body mass index, diabetes duration, medications used, history of coronary artery disease and its complications, blood pressure (systolic and diastolic), fasting plasma glucose, hemoglobin A1c, total cholesterol, low- and high-density lipoproteins, triglycerides, plasma creatinine, and 24-h urine albumin excretion.Results: The groups were statistically similar in all variables except diabetes duration (P = 0.037), ACE activity (P < 0.001), and ACE genotype (P = 0.008). The DD genotype was significantly more common in Group A (32.6% versus...
TL;DR: A case of a 25-year-old male with bilateral granulomatous panuveitis who after initial investigation and treatment for an infectious cause was determined to have autoimmune-related uveitis is described, suggestive of a role in autoimmunity, which is a known phenomenon in del22q11.2 syndrome.
Abstract: Purpose: Del22q11.2, also known as DiGeorge syndrome, has a spectrum of ocular, facial and systemic features. Despite features of T cell dysfunction, infection and autoimmunity (including juvenile idiopathic arthritis), uveitis has not been described in patients with DiGeorge syndrome.Methods: We describe a case of a 25-year-old male with bilateral granulomatous panuveitis who after initial investigation and treatment for an infectious cause was determined to have autoimmune-related uveitis with evidence on clinical, laboratory and imaging assessments suggestive of ocular sarcoidosis.Results: The patient was found to have a normal T cell count and T cell proliferative response that was compared to a control patient, and phenotypes determined by flow cytometry were normal. However, the CD4/CD8 ratio in this patient was slightly lower than normal and the number of CD28 negative T cells, in both CD4 and CD8 populations, were significantly higher than a control.Conclusions: The significance of these T cell ab...
TL;DR: In this article, a familial case of Blau syndrome associated with a CARD15/NOD2 mutation was reported, which is a rare autosomal dominant disorder characterized by early onset granulomatous arthritis, uveitis, skin rash and camptodactyly.
Abstract: Purpose: Blau syndrome is a rare autosomal dominant disorder characterized by early onset granulomatous arthritis, uveitis, skin rash and camptodactyly. We report a familial case of Blau syndrome associated with a CARD15/NOD2 mutation.Methods: PCR amplification and automated DNA sequencing of the complete CARD15/NOD2 coding sequence was performed.Results: Molecular analysis in affected subjects disclosed a heterozygous c.1147G>C point mutation in CARD15/NOD2 exon 4, that predicts a p.E383K change at the protein level.Conclusions: Blau syndrome should be considered in the differential diagnosis of childhood uveitis and the genetic analysis of the CARD15/NOD2 gene is helpful in the diagnosis.
TL;DR: Mutations in PITPNM3 do not appear to be a major cause of cone or cone-rod dystrophy, and four sequence variants, two missence mutations and two intronic changes were identified in the screen.
Abstract: 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.
TL;DR: Lack of association of PRKCB1 gene promoter polymorphisms and moderate protective association of PEDF gene polymorphism with DR in the south Indian population is suggested.
Abstract: Purpose: Polymorphisms in protein kinase C β (PRKCB1) and pigment epithelium derived factor (PEDF) genes have been associated with diabetic nephropathy and retinopathy respectively. Association of promoter polymorphisms–1504C/T and–1440G/T in PRKCB1 gene and sequence variations in exon 4 of PEDF gene are studied with diabetic retinopathy (DR) in a south Indian population based cohort.Methods: Type 2 diabetic patients with and without retinopathy (DR+ and DR- respectively) were recruited. The promoter region of PRKCB1 gene and exon 4 of PEDF genes were sequenced by polymerase chain reaction based direct sequencing and their frequencies were analyzed using relevant statistical tests.Results: The genotype and alleles of the two promoter polymorphisms of PRKCB1 gene were uniformly distributed among DR+ and DR- and hence were not associated with the disease. The haplotypes were also not significantly associated with DR. A T130T polymorphism observed in the PEDF gene showed modest association with absence of di...
TL;DR: A mother who is a phenotypically normal carrier of an autosomal recessive Wolfram syndrome gene and a father who has some of the findings of the syndrome and carries a single mutation that appears to be responsible for his hearing loss and optic atrophy are reported on.
Abstract: Background: Wolfram syndrome is characterized by optic atrophy, insulin dependent diabetes mellitus, diabetes insipidus and deafness. There are several other associated conditions reported in the literature, but congenital or early childhood cataracts are not among them.Materials and methods: Observational case series with confirmatory genetic analysis.Results: A pair of siblings, followed over 17 years, who manifest congenital or early childhood cataracts, diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. They are both compound heterozygotes for mutations (V415 deletion and A684V substitution) in the WFS1 gene. Their father has congenital sensorineural hearing loss and developed optic atrophy. He is heterozygous for A684V in WFS1.Conclusions: Wolfram syndrome should be in the differential diagnosis of genetic syndromes associated with congenital and early childhood cataracts. Here, we report on a mother who is a phenotypically normal carrier of an autosomal recessive Wolfram syndrome ge...
TL;DR: A case of interstitial 11q deletion in a 16 year-old female with associated systemic and craniofacial abnormalities as well as a novel combination of ocular findings, specifically strabismus, high myopia, bilateral cataracts, and bilateral total retinal detachments is described.
Abstract: Purpose: Jacobsen syndrome, also known as 11q deletion syndrome, is a rare condition characterized by multiple anomalies, including developmental delay, cardiac abnormalities, blood dyscrasias, distal limb abnormalities, craniofacial anomalies, and variable ophthalmic manifestations. The syndrome’s phenotype is due to a terminal deletion and is usually severely debilitating, frequently associated with fatality. Interstitial deletions, not involving the terminal end, have been associated with a more variable and less severe phenotype.Methods: Herein, we describe a case of interstitial 11q deletion in a 16 year-old female with associated systemic and craniofacial abnormalities as well as a novel combination of ocular findings, specifically strabismus, high myopia, bilateral cataracts, and bilateral total retinal detachments.Results: This case report highlights the necessity for a detailed ophthalmic examination of patients with both interstitial and terminal deletions of the long arm of chromosome 11.
TL;DR: This case supports the association between Pfeiffer syndrome and severe ocular anterior segment anomalies, including glaucoma, and underscores the possible role that FGFR2 has in development of the anterior segment of the eye.
Abstract: Purpose: To report a case of a child with Pfeiffer syndrome, unique ocular anterior segment findings and a mutation in FGFR2 (Trp290Cys).Methods: Case Report.Results: We describe a patient with Pfeiffer syndrome with a unique constellation of ocular anterior segment anomalies including microcornea, limbal scleralization, corectopia and glaucoma. Genomic DNA extraction was heterozygous for a G to T mutation at nucleotide 870 of the fibroblast growth factor receptor 2 gene (FGFR2) which changes tryptophan (TGG) to cysteine (TGT) at amino acid position 290 (Trp290Cys).Conclusion: This case supports the association between Pfeiffer syndrome and severe ocular anterior segment anomalies, including glaucoma, and underscores the possible role that FGFR2 has in development of the anterior segment of the eye.
TL;DR: This is the first clinical demonstration of supraciliary effusion in recurrent retinoblastoma and brachytherapy appears to be effective in the treatment of this type of recurrence.
Abstract: Purpose: A 2-year-old boy with syndromic bilateral retinoblastoma resulting from a (del(13)(q12.3q14.3)) developed a recurrent tumor measuring 2.3X2.3mm at the ora serrata 15 months following last treatment.Methods: Ultrasound biomicroscopy (UBM) revealed a mass invading the ciliary body 6.6 mm in diameter associated with a localized supraciliary effusion.Results: Complete tumor regression was achieved 1 month after brachytherapy with a 106Ruthenium plaque. There was no recurrence at 16 months.Conclusion: This is the first clinical demonstration of supraciliary effusion in recurrent retinoblastoma. Brachytherapy appears to be effective in the treatment of this type of recurrence.
TL;DR: The results provide further evidence to suggest that MIDD represents only a part of a continuous spectrum of disease related to the m.3243A>G point mutation in the tRNALeu gene.
Abstract: Purpose: To report ptosis as an associated finding in 2 patients with maternally inherited diabetes and deafness (MIDD).Methods: Two unrelated female patients with genetically proven MIDD are described. A complete ophthalmological examination included evaluation of levator muscle function, vertical fissure height and upper lid crease position measurements, the ice pack test and extensive imaging. In addition, pathology of the levator muscle was performed in 1 patient.Results: The first patient had an asymmetric ptosis at presentation. Levator muscle function was initially normal and decreased 3 years after, suggestive of a myogenic ptosis. Fundus examination revealed a macular pattern dystrophy. The second MIDD patient was referred for bilateral pigment alterations at the posterior pole. Gradually bilateral ptosis developed over a 3-year period. In both patients, ocular motility testing revealed a reduced upgaze.Conclusions: Myogenic ptosis has been described in association with several of the phenotypes ...