A Novel PITX2 Mutation and a Polymorphism in a 5-Generation Family with Axenfeld–Rieger Anomaly and Coexisting Fuchs’ Endothelial Dystrophy

Kniestedt, Christoph; Taralczak, Malgorzata; Thiel, Michael; Stuermer, Joerg; Baumer, Alessandra; Gloor, B.

doi:10.1016/j.ophtha.2006.05.017

Cited by 20 publications

(13 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although several rare mutations causing familial, early-onset FECD and rare variants associated with late-onset FECD have been identified [13], [14], [27], [30], [38]–[40], [56], [57], our current knowledge of the heritable causes of late-onset FECD is severely limited. No causal variant has been identified that is common in the population and that is of relatively modest effect.…”

Section: Discussionmentioning

confidence: 99%

“…SNPs were chosen from published reports on the genetics of FECD and related diseases of the cornea [14], [15], [30], [32], [34]–[38]. We selected two genes that have previously been associated with FECD: COL8A2 [13], [14], [39], [40] and TCF4 [15]–[19].…”

Section: Methodsmentioning

confidence: 99%

“…We selected two genes that have previously been associated with FECD: COL8A2 [13], [14], [39], [40] and TCF4 [15]–[19]. We also selected genes predominantly associated with PPCD ( ZEB1 ) [35], [41]–[43], CHED ( SLC4A11 ) [37], [44], [45], Axenfeld-Reiger Syndrome ( PITX2 ) [30], [31], brittle cornea syndrome ( ZNF469 ) [46], [47] and with central corneal thickness ( COL5A1 [24], [33], AVGR8 [33], FOXO1 [32], [33], AKAP6 [24], and AKAP13 [33]). …”

Section: Methodsmentioning

confidence: 99%

“…Given that we examined genes for all three disorders, we also examined the phenotype of CCT to determine if these genes do play a role in Fuchs dystrophy by moderating the thickness or thinness of the cornea. Mutations in PITX2 , a developmental regulatory gene, have shown association with FECD [30], corneal thinning [31] and Axenfeld-Rieger syndrome [30], [31]. Several other genes have been identified through genetic association studies as potential determinants of CCT [24], [32], [33], but have not been extensively tested in FECD patients (Table 1).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Differing Roles for TCF4 and COL8A2 in Central Corneal Thickness and Fuchs Endothelial Corneal Dystrophy

et al. 2012

View full text Add to dashboard Cite

Fuchs endothelial corneal dystrophy (FECD) is the most common late-onset, vision-threatening corneal dystrophy in the United States, affecting about 4% of the population. Advanced FECD involves a thickening of the cornea from stromal edema and changes in Descemet membrane. To understand the relationship between FECD and central corneal thickness (CCT), we characterized common genetic variation in COL8A2 and TCF4, genes previously implicated in CCT and/or FECD. Other genes previously associated with FECD (PITX2, ZEB1, SLC4A11), and genes only known to affect CCT (COL5A1, FOXO1, AVGR8, ZNF469) were also interrogated. FECD probands, relatives and controls were recruited from 32 clinical sites; a total of 532 cases and 204 controls were genotyped and tested for association of FECD case/control status, a 7-step FECD severity scale and CCT, adjusting for age and sex. Association of FECD grade with TCF4 was highly significant (OR = 6.01 at rs613872; p = 4.8×10−25), and remained significant when adjusted for changes in CCT (OR = 4.84; p = 2.2×10−16). Association of CCT with TCF4 was also significant (p = 6.1×10−7), but was abolished with adjustment for FECD grade (p = 0.92). After adjusting for FECD grade, markers in other genes examined were modestly associated (p ∼ 0.001) with FECD and/or CCT. Thus, common variants in TCF4 appear to influence FECD directly, and CCT secondarily via FECD. Additionally, changes in corneal thickness due to the effect of other loci may modify disease severity, age-at-onset, or other biomechanical characteristics.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Differing Roles for TCF4 and COL8A2 in Central Corneal Thickness and Fuchs Endothelial Corneal Dystrophy

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Later on, Kniestedt et al showed very similar ocular findings presented in a five generation family with a PITX2 mutation and polymorphism 20 .…”

Section: Discussionmentioning

confidence: 55%

Axenfeld-Rieger anomaly and corneal endothelial dystrophy: a case series

Oliveira¹,

Mitraud²,

Yamane³

2008

Rev. bras.oftalmol.

View full text Add to dashboard Cite

Report of a study of a family with a remarkable combination of endothelial corneal dystrophy, and anterior chamber dysgenesis classified as Axenfeld-Rieger anomaly. A 56 year-old female had blurred vision complaints. A slit lamp evaluation showed a bilateral posterior embryotoxon and guttata with corneal edema, Descemet membrane's folds, characterizing Fuchs endothelial dystrophy. A 27 year-old daughter was asymptomatic. The biomicroscopic exam disclosed a bilateral nasal and temporal posterior embryotoxon and a central guttata. Gonioscopy showed iridocorneal strands with a prominent Schwalbe´s line. The intraocular pressure was normal. Her sister, a 25 year-old female presented very similar abnormalities along with her brother (22 years old). A 19 year-old female sister presented the iridocorneal angle alterations, without Fuchs endothelial dystrophy, until this moment. This paper presents a family with a central cornea guttata or Fuchs dystrophy associated with Axenfeld-Rieger anomaly. Two different inherited diseases appearing together in an entire family may suggest a single molecular and genetic etiology, with high penetrance.

show abstract

Corneal Haze Determined by Confocal Microscopy 2 Years After Descemet Stripping With Endothelial Keratoplasty for Fuchs Corneal Dystrophy

Baratz¹,

McLaren²,

Maguire³

et al. 2012

Arch Ophthalmol

View full text Add to dashboard Cite

show abstract

A Novel PITX2 Mutation and a Polymorphism in a 5-Generation Family with Axenfeld–Rieger Anomaly and Coexisting Fuchs’ Endothelial Dystrophy

Cited by 20 publications

References 27 publications

Differing Roles for TCF4 and COL8A2 in Central Corneal Thickness and Fuchs Endothelial Corneal Dystrophy

Differing Roles for TCF4 and COL8A2 in Central Corneal Thickness and Fuchs Endothelial Corneal Dystrophy

Axenfeld-Rieger anomaly and corneal endothelial dystrophy: a case series

Corneal Haze Determined by Confocal Microscopy 2 Years After Descemet Stripping With Endothelial Keratoplasty for Fuchs Corneal Dystrophy

Contact Info

Product

Resources

About