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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

Sequencing results of the two novel mutations c.1702G>C and 1706T>A (p.Arg514Pro and Phe515Leu) of TGFBI in Family 1, and their corresponding normal sequences. Arrows indicate the mutation positions. Underlines highlight the codons that contain the mutations.
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f6: Sequencing results of the two novel mutations c.1702G>C and 1706T>A (p.Arg514Pro and Phe515Leu) of TGFBI in Family 1, and their corresponding normal sequences. Arrows indicate the mutation positions. Underlines highlight the codons that contain the mutations.

Mentions: Pedigree analysis showed an autosomal dominant inheritance pattern in all three families. In Family 1, two novel mutations, c.1702G>C and 1706T>A (p.Arg514Pro and Phe515Leu), in exon 11 of TGFBI (Figure 6) were identified in two of the patients (III-2 and III-4) examined, but were absent in the 4 unaffected members available for the analysis (III-3, IV-1, IV-2, and IV-3). In Family 2, a known hotspot mutation, c. 531C>T (p. Arg124Cys), in exon 4 was detected (Figure 7). A recently reported mutation [8], c.1876A>G (p.His572Arg), in exon 13 was identified in the proband of Family 3 (Figure 8).


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)

Sequencing results of the two novel mutations c.1702G>C and 1706T>A (p.Arg514Pro and Phe515Leu) of TGFBI in Family 1, and their corresponding normal sequences. Arrows indicate the mutation positions. Underlines highlight the codons that contain the mutations.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Sequencing results of the two novel mutations c.1702G>C and 1706T>A (p.Arg514Pro and Phe515Leu) of TGFBI in Family 1, and their corresponding normal sequences. Arrows indicate the mutation positions. Underlines highlight the codons that contain the mutations.
Mentions: Pedigree analysis showed an autosomal dominant inheritance pattern in all three families. In Family 1, two novel mutations, c.1702G>C and 1706T>A (p.Arg514Pro and Phe515Leu), in exon 11 of TGFBI (Figure 6) were identified in two of the patients (III-2 and III-4) examined, but were absent in the 4 unaffected members available for the analysis (III-3, IV-1, IV-2, and IV-3). In Family 2, a known hotspot mutation, c. 531C>T (p. Arg124Cys), in exon 4 was detected (Figure 7). A recently reported mutation [8], c.1876A>G (p.His572Arg), in exon 13 was identified in the proband of Family 3 (Figure 8).

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