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Different phenotypes of lattice corneal dystrophy type I in patients with 417C>T (R124C) and 1762A>G (H572R) mutations in TGFBI (BIGH3).

Romero P, Moraga M, Herrera L - Mol. Vis. (2010)

Bottom Line: In Family Two, the mutation was a de novo mutation, as neither parent was a carrier.Screening by sequencing analysis for mutation in exons 11, 12, 13, and 14 in the affected patient in Family Three revealed a heterozygous A1762G mutation (H572R) in exon 13.This is the second report of the 417C>T mutation and the first report of 1762 A>G mutation (H572R) in Chilean patients.

View Article: PubMed Central - PubMed

Affiliation: Depto. de Oftalmología, Hospital Clínico José Joaquín Aguirre, Universidad de Chile, Santiago, Chile.

ABSTRACT

Purpose: To describe clinical data and to characterize mutations in the transforming growth factor beta-induced (TGFBI) gene in patients from three unrelated Chilean families with lattice corneal dystrophy type I (LCDI).

Methods: Snellen acuity tests, anterior segment slit lamp examinations, dilated fundus evaluations, and tonometry were performed for seven patients--five females and two males belonging to three unrelated families--affected with lattice corneal dystrophy Type I. Genomic DNA was also extracted from peripheral leukocytes from the seven patients and four healthy relatives. The 417C>T mutation (R124C) was screened using PCR-RFLP for the seven patients and four healthy relatives. Exons 11, 12, 13, and 14 were sequenced in one patient not carrying the mutation in codon 124. Comparison of phenotype to genotype was performed.

Results: The seven patients studied exhibited LCDI in both eyes, most of which were symmetric. Affected individuals demonstrated progression from central subepithelial needlelike deposits and polymorphic anterior stromal opacities. The age at onset of symptoms varied between six to 15 years old in Family One; the patient in Family Two was five years old and the patient in Family Three was 21 years old. Visual acuity varied from 1.0 to 0.05. Two patients, aged 50 and 45 years, underwent penetrating keratoplasty in both eyes, and two patients, aged 47 and 24 years, underwent penetrating keratoplasty in one eye. The only patient in Family Three exhibited a somewhat distinct phenotype, with yellowish discoloration in the anterior stroma and fewer, but thicker lattice lines than the patients in Families One and Two. Screening for the mutation C>T at the nucleotide position 417 (R124C) in exon 4 in the three families revealed the heterozygous R124C mutation in Families One and Two. In Family Two, the mutation was a de novo mutation, as neither parent was a carrier. Screening by sequencing analysis for mutation in exons 11, 12, 13, and 14 in the affected patient in Family Three revealed a heterozygous A1762G mutation (H572R) in exon 13.

Conclusions: This is the second report of the 417C>T mutation and the first report of 1762 A>G mutation (H572R) in Chilean patients. The H572R mutation identified is associated with a distinct lattice corneal dystrophy type I phenotype.

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Related in: MedlinePlus

Photographs of the cornea from six individuals examined using slit lamp examination. Slit lamp photographs of patient V-19 of Family One at 27 years of age show opacities in the central stroma and linear forms in the left cornea (A and B; A: OD and B: OS). The image of case III-1 shows irregularity of the epithelial surface with subepithelial and anterior stromal scarring in the left eye (C). The image of case IV-10 revealed the presence of a network of linear opacities associated with polymorphic anterior stromal opacities in the right eye (D). The image of case IV-13 at 50 years of age shows opacities in the central stroma and linear forms in the left cornea (E). The image of case II-1 of Family Two at age 25 shows a network of linear opacities associated with other smaller opaque spots and refractile lattice lines in the left eye (F) and the right eye shows penetrating keratoplasty with characteristic mydriasis of Urrets-Zavalia syndrome (G). The photographs of case I-1 of Family Three at 52 years of age show thick lattice lines and yellowish discoloration in the anterior stroma, resulting in clouding of the central cornea (H and I).
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f2: Photographs of the cornea from six individuals examined using slit lamp examination. Slit lamp photographs of patient V-19 of Family One at 27 years of age show opacities in the central stroma and linear forms in the left cornea (A and B; A: OD and B: OS). The image of case III-1 shows irregularity of the epithelial surface with subepithelial and anterior stromal scarring in the left eye (C). The image of case IV-10 revealed the presence of a network of linear opacities associated with polymorphic anterior stromal opacities in the right eye (D). The image of case IV-13 at 50 years of age shows opacities in the central stroma and linear forms in the left cornea (E). The image of case II-1 of Family Two at age 25 shows a network of linear opacities associated with other smaller opaque spots and refractile lattice lines in the left eye (F) and the right eye shows penetrating keratoplasty with characteristic mydriasis of Urrets-Zavalia syndrome (G). The photographs of case I-1 of Family Three at 52 years of age show thick lattice lines and yellowish discoloration in the anterior stroma, resulting in clouding of the central cornea (H and I).

Mentions: The proband, a 27-year-old woman, began with episodes of acute ocular pain, redness, and photophobia at six years of age. The frequency and severity of these episodes increased coincident with a gradual deterioration of vision in both eyes. Slit lamp examination showed the presence of large, typical fine branching lattice lines in the anterior stroma of both eyes (Figure 2A,B). A clear area was preserved around the corneal-scleral limbus. She showed a network of linear opacities associated with other smaller opaque spots and refractile lattice lines. No vascularization of the cornea was observed. Central corneal sensation was reduced. Best-corrected vision was 0.8 in the right eye (OD) and 0.7 in the left eye (OS).


Different phenotypes of lattice corneal dystrophy type I in patients with 417C>T (R124C) and 1762A>G (H572R) mutations in TGFBI (BIGH3).

Romero P, Moraga M, Herrera L - Mol. Vis. (2010)

Photographs of the cornea from six individuals examined using slit lamp examination. Slit lamp photographs of patient V-19 of Family One at 27 years of age show opacities in the central stroma and linear forms in the left cornea (A and B; A: OD and B: OS). The image of case III-1 shows irregularity of the epithelial surface with subepithelial and anterior stromal scarring in the left eye (C). The image of case IV-10 revealed the presence of a network of linear opacities associated with polymorphic anterior stromal opacities in the right eye (D). The image of case IV-13 at 50 years of age shows opacities in the central stroma and linear forms in the left cornea (E). The image of case II-1 of Family Two at age 25 shows a network of linear opacities associated with other smaller opaque spots and refractile lattice lines in the left eye (F) and the right eye shows penetrating keratoplasty with characteristic mydriasis of Urrets-Zavalia syndrome (G). The photographs of case I-1 of Family Three at 52 years of age show thick lattice lines and yellowish discoloration in the anterior stroma, resulting in clouding of the central cornea (H and I).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2927433&req=5

f2: Photographs of the cornea from six individuals examined using slit lamp examination. Slit lamp photographs of patient V-19 of Family One at 27 years of age show opacities in the central stroma and linear forms in the left cornea (A and B; A: OD and B: OS). The image of case III-1 shows irregularity of the epithelial surface with subepithelial and anterior stromal scarring in the left eye (C). The image of case IV-10 revealed the presence of a network of linear opacities associated with polymorphic anterior stromal opacities in the right eye (D). The image of case IV-13 at 50 years of age shows opacities in the central stroma and linear forms in the left cornea (E). The image of case II-1 of Family Two at age 25 shows a network of linear opacities associated with other smaller opaque spots and refractile lattice lines in the left eye (F) and the right eye shows penetrating keratoplasty with characteristic mydriasis of Urrets-Zavalia syndrome (G). The photographs of case I-1 of Family Three at 52 years of age show thick lattice lines and yellowish discoloration in the anterior stroma, resulting in clouding of the central cornea (H and I).
Mentions: The proband, a 27-year-old woman, began with episodes of acute ocular pain, redness, and photophobia at six years of age. The frequency and severity of these episodes increased coincident with a gradual deterioration of vision in both eyes. Slit lamp examination showed the presence of large, typical fine branching lattice lines in the anterior stroma of both eyes (Figure 2A,B). A clear area was preserved around the corneal-scleral limbus. She showed a network of linear opacities associated with other smaller opaque spots and refractile lattice lines. No vascularization of the cornea was observed. Central corneal sensation was reduced. Best-corrected vision was 0.8 in the right eye (OD) and 0.7 in the left eye (OS).

Bottom Line: In Family Two, the mutation was a de novo mutation, as neither parent was a carrier.Screening by sequencing analysis for mutation in exons 11, 12, 13, and 14 in the affected patient in Family Three revealed a heterozygous A1762G mutation (H572R) in exon 13.This is the second report of the 417C>T mutation and the first report of 1762 A>G mutation (H572R) in Chilean patients.

View Article: PubMed Central - PubMed

Affiliation: Depto. de Oftalmología, Hospital Clínico José Joaquín Aguirre, Universidad de Chile, Santiago, Chile.

ABSTRACT

Purpose: To describe clinical data and to characterize mutations in the transforming growth factor beta-induced (TGFBI) gene in patients from three unrelated Chilean families with lattice corneal dystrophy type I (LCDI).

Methods: Snellen acuity tests, anterior segment slit lamp examinations, dilated fundus evaluations, and tonometry were performed for seven patients--five females and two males belonging to three unrelated families--affected with lattice corneal dystrophy Type I. Genomic DNA was also extracted from peripheral leukocytes from the seven patients and four healthy relatives. The 417C>T mutation (R124C) was screened using PCR-RFLP for the seven patients and four healthy relatives. Exons 11, 12, 13, and 14 were sequenced in one patient not carrying the mutation in codon 124. Comparison of phenotype to genotype was performed.

Results: The seven patients studied exhibited LCDI in both eyes, most of which were symmetric. Affected individuals demonstrated progression from central subepithelial needlelike deposits and polymorphic anterior stromal opacities. The age at onset of symptoms varied between six to 15 years old in Family One; the patient in Family Two was five years old and the patient in Family Three was 21 years old. Visual acuity varied from 1.0 to 0.05. Two patients, aged 50 and 45 years, underwent penetrating keratoplasty in both eyes, and two patients, aged 47 and 24 years, underwent penetrating keratoplasty in one eye. The only patient in Family Three exhibited a somewhat distinct phenotype, with yellowish discoloration in the anterior stroma and fewer, but thicker lattice lines than the patients in Families One and Two. Screening for the mutation C>T at the nucleotide position 417 (R124C) in exon 4 in the three families revealed the heterozygous R124C mutation in Families One and Two. In Family Two, the mutation was a de novo mutation, as neither parent was a carrier. Screening by sequencing analysis for mutation in exons 11, 12, 13, and 14 in the affected patient in Family Three revealed a heterozygous A1762G mutation (H572R) in exon 13.

Conclusions: This is the second report of the 417C>T mutation and the first report of 1762 A>G mutation (H572R) in Chilean patients. The H572R mutation identified is associated with a distinct lattice corneal dystrophy type I phenotype.

Show MeSH
Related in: MedlinePlus