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Novel and known mutations of TGFBI, their genotype-phenotype correlation and structural modeling in 3 Chinese families with lattice corneal dystrophy.

Zhong X, Chen S, Huang W, Yang J, Chen X, Zhou Y, Zhou Q, Wang Y - Mol. Vis. (2010)

Bottom Line: Structural modeling revealed changes in the 2nd structure of the mutant proteins, but did not detect gross structural changes.Arg124Cys) were associated with more severe LCD phenotypes in the families.These results provide more data for molecular diagnosis and prognosis of the disease.

View Article: PubMed Central - PubMed

Affiliation: Zhongshan Ophthalmic Center and State Key laboratory of ophthalmology, Sun Yat-Sen University, Guangzhou, P.R.China.

ABSTRACT

Purpose: To report novel transforming growth factor beta-induced (TGFBI) mutations responsible for lattice corneal dystrophy (LCD), the associated genotype-phenotype correlation, and structural changes in the mutant proteins in three Chinese families.

Methods: Three unrelated Chinese families were diagnosed as Type I LCD. Mutations in TGFBI were detected by sequencing all of the 17 exons and splice sites of the gene. Phenotype, including corneal erosions, and opacification in the families were compared. Structural changes of the mutant proteins were modeled. One hundred healthy volunteers were recruited as controls for sequence analysis of TGFBI.

Results: Two novel mutations, c.(1702G>C and 1706T>A; p.Arg514Pro and Phe515Leu) in TGFBI were identified in Family 1. Two known hotspot mutations, c. 531C>T (p. Arg124Cys) and c.1876A>G (p.His572Arg), were revealed in Family 2 and Family 3, respectively. Sequence analysis in the 100 healthy control subjects, the unaffected members in Family 1, and evolutionary alignment showed that the novel mutations occurred in the conserved amino acids. Structural modeling revealed changes in the 2nd structure of the mutant proteins, but did not detect gross structural changes. Mutations c.(1702G>C and 1706T>A; p.Arg514Pro and Phe515Leu) and the c. 531C>T (p. Arg124Cys) were present in the corneas with sever opacification.

Conclusions: The novel mutations c.(1702G>C and 1706T>A; p.Arg514Pro and Phe515Leu), c. 531C>T (p. Arg124Cys), c.1876A>G (p.His572Arg) in TGFBI were responsible for LCD in the 3 families. Mutations c.(1702G>C and 1706T>A) (p.Arg514Pro and Phe515Leu) and the c. 531C>T (p. Arg124Cys) were associated with more severe LCD phenotypes in the families. These results provide more data for molecular diagnosis and prognosis of the disease.

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Related in: MedlinePlus

Clinical photographs of corneas in one affected member (I-1) in Family 2 at 63 years of age. The right eye (A) contained opacifications from presumed recurrent disease 20 years after a penetrating keratoplasty. The left eye (B) showed a corneal implant that was transparent after a penetrating keratoplasty 10 years ago. This eye compounded with the primary cataract and the corrected visual acuity with pinhole is 20/32.
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f4: Clinical photographs of corneas in one affected member (I-1) in Family 2 at 63 years of age. The right eye (A) contained opacifications from presumed recurrent disease 20 years after a penetrating keratoplasty. The left eye (B) showed a corneal implant that was transparent after a penetrating keratoplasty 10 years ago. This eye compounded with the primary cataract and the corrected visual acuity with pinhole is 20/32.

Mentions: The proband (II-4) patient in Family 2 had visual loss in both eyes when she was approximately 23 years old. On examination, subepithelial punctiform corneal erosions were present in both eyes (Figure 3). In 1985, her father (I-1) had penetrating keratoplasty for the first time on his right eye at age 41. One year later, the corneal implant was rejected. He had penetrating keratoplasty twice in both eyes one year later. Due to recurrence of the primary disease, he had another penetrating keratoplasty on his left eye ten years later (Figure 4). Unfortunately, his histopathological record could not be retrieved. Her son (III-3) experienced a foreign body sensation in both eyes, however, no abnormalities were found in his corneas.


Novel and known mutations of TGFBI, their genotype-phenotype correlation and structural modeling in 3 Chinese families with lattice corneal dystrophy.

Zhong X, Chen S, Huang W, Yang J, Chen X, Zhou Y, Zhou Q, Wang Y - Mol. Vis. (2010)

Clinical photographs of corneas in one affected member (I-1) in Family 2 at 63 years of age. The right eye (A) contained opacifications from presumed recurrent disease 20 years after a penetrating keratoplasty. The left eye (B) showed a corneal implant that was transparent after a penetrating keratoplasty 10 years ago. This eye compounded with the primary cataract and the corrected visual acuity with pinhole is 20/32.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2822555&req=5

f4: Clinical photographs of corneas in one affected member (I-1) in Family 2 at 63 years of age. The right eye (A) contained opacifications from presumed recurrent disease 20 years after a penetrating keratoplasty. The left eye (B) showed a corneal implant that was transparent after a penetrating keratoplasty 10 years ago. This eye compounded with the primary cataract and the corrected visual acuity with pinhole is 20/32.
Mentions: The proband (II-4) patient in Family 2 had visual loss in both eyes when she was approximately 23 years old. On examination, subepithelial punctiform corneal erosions were present in both eyes (Figure 3). In 1985, her father (I-1) had penetrating keratoplasty for the first time on his right eye at age 41. One year later, the corneal implant was rejected. He had penetrating keratoplasty twice in both eyes one year later. Due to recurrence of the primary disease, he had another penetrating keratoplasty on his left eye ten years later (Figure 4). Unfortunately, his histopathological record could not be retrieved. Her son (III-3) experienced a foreign body sensation in both eyes, however, no abnormalities were found in his corneas.

Bottom Line: Structural modeling revealed changes in the 2nd structure of the mutant proteins, but did not detect gross structural changes.Arg124Cys) were associated with more severe LCD phenotypes in the families.These results provide more data for molecular diagnosis and prognosis of the disease.

View Article: PubMed Central - PubMed

Affiliation: Zhongshan Ophthalmic Center and State Key laboratory of ophthalmology, Sun Yat-Sen University, Guangzhou, P.R.China.

ABSTRACT

Purpose: To report novel transforming growth factor beta-induced (TGFBI) mutations responsible for lattice corneal dystrophy (LCD), the associated genotype-phenotype correlation, and structural changes in the mutant proteins in three Chinese families.

Methods: Three unrelated Chinese families were diagnosed as Type I LCD. Mutations in TGFBI were detected by sequencing all of the 17 exons and splice sites of the gene. Phenotype, including corneal erosions, and opacification in the families were compared. Structural changes of the mutant proteins were modeled. One hundred healthy volunteers were recruited as controls for sequence analysis of TGFBI.

Results: Two novel mutations, c.(1702G>C and 1706T>A; p.Arg514Pro and Phe515Leu) in TGFBI were identified in Family 1. Two known hotspot mutations, c. 531C>T (p. Arg124Cys) and c.1876A>G (p.His572Arg), were revealed in Family 2 and Family 3, respectively. Sequence analysis in the 100 healthy control subjects, the unaffected members in Family 1, and evolutionary alignment showed that the novel mutations occurred in the conserved amino acids. Structural modeling revealed changes in the 2nd structure of the mutant proteins, but did not detect gross structural changes. Mutations c.(1702G>C and 1706T>A; p.Arg514Pro and Phe515Leu) and the c. 531C>T (p. Arg124Cys) were present in the corneas with sever opacification.

Conclusions: The novel mutations c.(1702G>C and 1706T>A; p.Arg514Pro and Phe515Leu), c. 531C>T (p. Arg124Cys), c.1876A>G (p.His572Arg) in TGFBI were responsible for LCD in the 3 families. Mutations c.(1702G>C and 1706T>A) (p.Arg514Pro and Phe515Leu) and the c. 531C>T (p. Arg124Cys) were associated with more severe LCD phenotypes in the families. These results provide more data for molecular diagnosis and prognosis of the disease.

Show MeSH
Related in: MedlinePlus