TGFBI Gene Mutation Analysis in Families with Hereditary Corneal Dystrophies from Ukraine

Pampukha, V. M.; Drozhyna, Galyna I; Лившиц, Л. А.

doi:10.1159/000080945

Cited by 8 publications

(8 citation statements)

References 18 publications

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“…Specific mutations of the TGFBI gene are associated with specific forms of corneal disorders, and the same genotype-phenotype correlation has been observed in patients of various ethnic backgrounds, including those from Ukraine [5, 14]. Our result, the newly identified mutation reported in this paper, expands the mutational spectrum in the group of TGFBI-linked CD, and may eventually lead to improved clinical diagnostics of patients with CD.…”

Section: Resultssupporting

confidence: 76%

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Novel L558P Mutation of the TGFBI Gene Found in Ukrainian Families with Atypical Corneal Dystrophy

Pampukha

Kravchenko²,

Tereshchenko³

et al. 2009

Ophthalmologica

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Purpose: To report a novel L558P mutation of the human transforming growth factor β-induced (TGFBI) gene found in Ukrainian families with atypical corneal dystrophy (CD). Methods: Genomic DNA was extracted from peripheral leukocytes of 12 members of 4 unrelated families with atypical CD. We performed genotype analysis of these families with microsatellite markers surrounding the TGFBI locus. Exons of the TGFBI gene were amplified by polymerase chain reaction (PCR), and directly sequenced in 5 patients of 4 unrelated families. We utilized a simple PCR/restriction fragment length polymorphism-based technique for L558P mutation identification. Fifty normal individuals were also analyzed as controls. These assays were complemented by histological analysis of available corneal buttons excised during penetrating keratoplasty. Results: A heterozygous single-base-pair transition (CTC to CCC, leucine to proline) at codon 558 in exon 12 of the TGFBI gene (L558P) was detected in 10 individuals. Eight are affected, and 2 are teenagers with no clinical manifestation of the disease as yet. The mutation was not found in 2 healthy individuals from 2 high-risk CD families, nor in 50 normal controls. Histopathological examination identified amyloid deposits, mostly in the posterior central cornea. Haplotype analysis provided evidence of a common founder of the L558P mutation. The mutation works on the protein level by disrupting an α-helix, which is crucial for the normal functioning of keratoepithelin. Conclusion: A novel L558P mutation in the TGFBI gene causes an atypical type of stromal CD.

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Section: Resultssupporting

confidence: 76%

“…We can make a suggestion based on these data that the first opacities appear between 18 and 37 years of age. We did not detect any known TGFBI mutations in all these patients [14]. …”

Section: Resultsmentioning

confidence: 99%

Novel L558P Mutation of the TGFBI Gene Found in Ukrainian Families with Atypical Corneal Dystrophy

Pampukha

Kravchenko²,

Tereshchenko³

et al. 2009

Ophthalmologica

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“…Munier et al [1997] discovered a mutation in exon 4 of the TGFBI gene corresponding to a change of c.370 C4T (Arg124Cys) in 14 individuals from two families with this phenotype. Subsequently, in most individuals with this particular corneal disorder throughout the world, the disorder has been attributed to the same mutation in this gene [Mashima et al, 1997;Gupta et al, 1998;Hotta et al, 1998;Meins et al, 1998;El Shabrawi et al, 1999;Korvatska et al, 1999, Fujiki et al, 2000Mashima et al, 2000;Yamamoto et al, 2000;Afshari et al, 2001;Dighiero et al, 2001;Hellenbroich et al, 2001;Kim et al, 2001;Ellies et al, 2002;Hirano et al, 2002;Pampukha et al, 2004].…”

Section: Lcd Type Imentioning

confidence: 99%

TGFBI gene mutations in corneal dystrophies

2006

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The lattice corneal dystrophies (LCD) and granular corneal dystrophies (GCD) are autosomal dominant disorders of the corneal stroma. They are bilateral, progressive conditions characterized by the formation of opacities arising due to the deposition of insoluble material in the corneal stroma leading to visual impairment. The LCDs and GCDs are distinguished from each other and are divided into subtypes on the basis of the clinical appearance of the opacities, clinical features of the disease, and on histopathological staining properties of the deposits. The GCDs and most types of LCD arise from mutations in the transforming growth factor beta-induced (TGFBI) gene on chromosome 5q31. Over 30 mutations causing LCD and GCD have been identified so far in the TGFBI. There are two mutation hotspots corresponding to arginine residues at positions 124 and 555 of the transforming growth factor beta induced protein (TGFBIp) and they are the most frequent sites of mutation in various populations. Mutations at either of these two hotspots result in specific types of LCD or GCD. The majority of identified mutations involve residues in the fourth fasciclin-like domain of TGFBIp.

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“…Some authors suggest that mutations could affect the tertiary structure of keratoepithelin causing the protein subunits to polymerize into different structures or that the modified domains could impair the binding of keratoepithelin to stromal proteins such as collagen type VI affecting the structural characteristics of the tissue. 4,6,10,15 Some studies indicate that mutations at amino acid R124 abolish a phosphorylation site that could affect the tertiary structure of keratoepithelin leading to amyloid formation. 4,20,22,23 Further studies are necessary to understand the role of keratoepithelin in normal corneal structure and function.…”

Section: Discussionmentioning

confidence: 99%

“…2,4,5 Mutations in the TGFBI gene have been described in patients from many nationalities. [7][8][9][10][11][12] We report the first series of Brazilian patients screened for mutations in the TGFBI gene.…”

Section: Introductionmentioning

confidence: 99%

TGFBI gene mutations in Brazilian patients with corneal dystrophy

Solari

Ventura

Perez

et al. 2006

Eye

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Purpose To investigate the transforming growth factor beta-induced gene (TGFBI) mutations in Brazilian patients with corneal dystrophy and to evaluate the phenotypegenotype correlation in these patients. Methods A total of 11 unrelated families were studied. The diagnosis of corneal dystrophy was based on clinical and histopathological findings. Genomic DNA was extracted from peripheral blood leucocytes, and exons 4 and 12 of the TGFBI gene were amplified by polymerase chain reaction followed by direct sequencing on both strands. Results Five different mutations in the TGFBI gene were found in the probands. We identified the following mutations: lattice corneal dystrophyFR124C and A546T; Reis-Bü cklers corneal dystrophyFR555Q and R124L; granular corneal dystrophyFR555W and Avellino dystrophyFR555W. In three of the 11 studied families there was no mutation in exons 4 and 12. Conclusions This is the first report of mutations in the TGFBI gene in a series of Brazilian patients with corneal dystrophy. The findings indicate that TGFBI gene screening should be considered in the diagnosis of corneal dystrophy.

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TGFBI Gene Mutation Analysis in Families with Hereditary Corneal Dystrophies from Ukraine

Cited by 8 publications

References 18 publications

Novel L558P Mutation of the TGFBI Gene Found in Ukrainian Families with Atypical Corneal Dystrophy

Novel L558P Mutation of the TGFBI Gene Found in Ukrainian Families with Atypical Corneal Dystrophy

TGFBI gene mutations in corneal dystrophies

TGFBI gene mutations in Brazilian patients with corneal dystrophy

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