Central corneal thickness is lower in osteogenesis imperfecta and negatively correlates with the presence of blue sclera

Evereklioğlu, Cem; Madenci, Ercan; Bayazıt, Yıldırım A.; Yılmaz, Kutluhan; Balat, Ayşe; Bekir, Necdet

doi:10.1046/j.1475-1313.2002.00062.x

Cited by 75 publications

(59 citation statements)

References 27 publications

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“…The PLOD1 gene encodes Procollagen-Lysine 2-oxoglutarate 5-dioxygenase, a lysyl hydroxylase. This enzyme is involved in the cross linking of collagen through hydroxylating lysyl residues (Giunta (Evereklioglu et al 2002;Pedersen and Bramsen 1984), and keratoconus is an acquired corneal thinning disease. Mutations in PLOD1 cause the kyphoscoliotic type of Ehlers-Danlos Syndrome.…”

Section: Candidate Gene Analysismentioning

confidence: 99%

Apparent autosomal dominant keratoconus in a large Australian pedigree accounted for by digenic inheritance of two novel loci

et al. 2008

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Keratoconus is a debilitating ocular disease characterised by progressive asymmetrical thinning of the cornea, the clear covering at the front of the eye. The resulting protrusion of the cornea results in severe refractive error, in the most severe cases requiring corneal grafting. It is a complex disease with a genetic component. Despite several reports of linked loci, major gene identification has been elusive. A genome-wide linkage scan in a large Australian pedigree with apparent autosomal dominant keratoconus was conducted using the Affymetrix 10K SNP chip and two regions of linkage identified. Functional candidate genes from within both linkage peaks were assessed for corneal expression and screened for mutations in affected family members. Equal evidence of linkage was detected to both 1p36.23-36.21 and 8q13.1-q21.11 with LOD scores of 1.9. Analysis of both loci concurrently suggests digenic linkage with two-locus LOD score of 3.4. All affected individuals carry identical haplotypes at both loci. Carriers of either linked haplotype without the other do not have keratoconus. No mutations were identified in the following candidate genes expressed in the cornea: ENO1, CTNNBIP1, PLOD1, UBIAD1, SPSB1 or TCEB1. Although the pedigree appears to demonstrate simple autosomal dominant inheritance, the disorder is actually genetically complex. This pedigree may provide a link between inherited forms of keratoconus and sporadic cases.

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Section: Candidate Gene Analysismentioning

confidence: 99%

Apparent autosomal dominant keratoconus in a large Australian pedigree accounted for by digenic inheritance of two novel loci

et al. 2008

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“…OI is a clinically heterogeneous disorder, manifested by a broad range of signs and symptoms with extreme variation in the degree of severity. Apart from its skeletal manifestations, other clinical Wndings can include hearing loss, dentinogenesis imperfecta, hyperlaxity of the ligaments and skin, blue sclerae and reduced central corneal thickness (CCT) (Pedersen and Bramsen 1984;Evereklioglu et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Novel quantitative trait loci for central corneal thickness identified by candidate gene analysis of osteogenesis imperfecta genes

et al. 2009

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Osteogenesis imperfecta (OI) is a rare connective tissue disorder caused by mutations in the type I collagen genes, COL1A1 and COL1A2, and is characterised by low bone mass and bone fragility. In this study, we explored the relationship between type 1 collagen genes and the quantitative trait central corneal thickness (CCT). CCT was measured in a cohort of 28 Australian type I OI patients and mean CCT was found to be significantly lower compared to a normal population (P < 0.001). We then investigated CCT and corneal collagen fibril diameter and density in a mouse model of OI with a col1a2 mutation. Mean CCT was significantly lower in mutant mice (P = 0.002), as was corneal collagen fibril diameter (P = 0.034), whilst collagen fibril density was significantly greater in mutants (P = 0.034). Finally, we conducted a genetic study to determine whether common single nucleotide polymorphisms (SNPs) in COL1A1 and COL1A2 are associated with CCT variation in the normal human population. Polymorphism rs2696297 (P = 0.003) in COL1A1 and a three SNP haplotype in COL1A2 (P = 0.007) were all significantly associated with normal CCT variation. These data implicate type 1 collagen in the determination of CCT in both OI patients and normal individuals. This provides the first evidence of quantitative trait loci that influence CCT in a normal population and has potential implications for investigating genes involved in glaucoma pathogenesis, a common eye disease in which the severity and progression is influenced by CCT.

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“…In OI, the presence of blue sclera is not associated with any significant ocular pathology [Zack et al, 2007]. A correlation between blue sclerae and reduced corneal thickness has been described [Evereklioglu et al, 2002] but has also been challenged by opposite findings [Sarathchandra et al, 1999]. In spite of also other explanations [Eichholtz and Müller, 1972;Lanting et al, 1985], the etiology of the blue sclerae in OI type I is unclear [Zack et al, 2007].…”

Section: Prenatal and Postnatal Diagnosis Of Oi With Clinical Examplesmentioning

confidence: 99%

Osteogenesis Imperfecta: A Review with Clinical Examples

Dijk

Cobben²,

Kariminejad³

et al. 2011

Mol Syndromol

185

129

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Osteogenesis imperfecta (OI) is characterized by susceptibility to bone fractures, with a severity ranging from subtle increase in fracture frequency to prenatal fractures. The first scientific description of OI dates from 1788. Since then, important milestones in OI research and treatment have, among others, been the classification of OI into 4 types (the ‘Sillence classification’), the discovery of defects in collagen type I biosynthesis as a cause of most cases of OI and the use of bisphosphonate therapy. Furthermore, in the past 5 years, it has become clear that OI comprises a group of heterogeneous disorders, with an estimated 90% of cases due to a causative variant in the COL1A1 or COL1A2 genes and with the remaining 10% due to causative recessive variants in the 8 genes known so far, or in other currently unknown genes. This review aims to highlight the current knowledge around the history, epidemiology, pathogenesis, clinical/radiological features, management, and future prospects of OI. The text will be illustrated with clinical descriptions, including radiographs and, where possible, photographs of patients with OI.

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Central corneal thickness is lower in osteogenesis imperfecta and negatively correlates with the presence of blue sclera

Cited by 75 publications

References 27 publications

Apparent autosomal dominant keratoconus in a large Australian pedigree accounted for by digenic inheritance of two novel loci

Apparent autosomal dominant keratoconus in a large Australian pedigree accounted for by digenic inheritance of two novel loci

Novel quantitative trait loci for central corneal thickness identified by candidate gene analysis of osteogenesis imperfecta genes

Osteogenesis Imperfecta: A Review with Clinical Examples

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