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Mutation Analysis of the TGFBI Gene in Consecutive Korean Patients With Corneal Dystrophies.

Song JS, Lim DH, Chung ES, Chung TY, Ki CS - Ann Lab Med (2015)

Bottom Line: Of particular note, one patient with rapidly progressive CD had the p.R124H mutation as well as a novel nonsense variant with unknown clinical significance (p.A179*).This study provides epidemiological insight into CDs in a Korean population and reaffirms that GCD2 is the most common TGFBI CD phenotype and that p.R124H is the only mutation identified in patients with GCD2.In addition, we broaden the spectrum of TGFBI mutations by identifying two novel missense variants in patients with LCD1.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

ABSTRACT

Background: Mutations in the transforming growth factor β-induced gene (TGFBI) are major causes of genetic corneal dystrophies (CDs), which can be grouped into TGFBI CDs. Although a few studies have reported the clinical and genetic features of Korean patients with TGFBI CD, no data are available regarding the frequency and spectrum of TGFBI mutations in a consecutive series of Korean patients with clinically diagnosed CDs.

Methods: Patients with any type of CD, who underwent both ophthalmologic examination and TGFBI gene analysis by Sanger sequencing at a tertiary care hospital in Seoul, Korea from 2006 to 2013, were enrolled in this study.

Results: Among a total of 89 patients, 77 (86.5%) were diagnosed as having clinical TGFBI CD. Seventy-three out of 74 patients (98.6%) with granular CD type 2 (GCD2), had the p.R124H mutation. Of particular note, one patient with rapidly progressive CD had the p.R124H mutation as well as a novel nonsense variant with unknown clinical significance (p.A179*). In three patients with lattice CD type 1 (LCD1), one known mutation (p.R124C) and two novel variants (p.L569Q and p.T621P) in the TGFBI gene were identified.

Conclusions: This study provides epidemiological insight into CDs in a Korean population and reaffirms that GCD2 is the most common TGFBI CD phenotype and that p.R124H is the only mutation identified in patients with GCD2. In addition, we broaden the spectrum of TGFBI mutations by identifying two novel missense variants in patients with LCD1.

No MeSH data available.


Related in: MedlinePlus

Sequence electrophoerograms of novel TGFBI variants. (A) The c.535C>T (p.A179*) variant identified in a patient with granular corneal dystrophy type 2 (arrow). (B) The c.1706T>A (p.L569Q) variant identified in a patient with lattice corneal dystrophy, TGFBI type (arrow). (C) The c.1861A>C (p.T621P) variant identified in a patient with lattice corneal dystrophy, TGFBI type (arrow).
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Figure 2: Sequence electrophoerograms of novel TGFBI variants. (A) The c.535C>T (p.A179*) variant identified in a patient with granular corneal dystrophy type 2 (arrow). (B) The c.1706T>A (p.L569Q) variant identified in a patient with lattice corneal dystrophy, TGFBI type (arrow). (C) The c.1861A>C (p.T621P) variant identified in a patient with lattice corneal dystrophy, TGFBI type (arrow).

Mentions: Among the 74 patients clinically diagnosed as having GCD2, 73 (82.0%, 73/89) had the p.R124H mutation, while one patient had no mutations in the TGFBI gene (Fig. 1). One patient with the p.R124H mutation had an additional nonsense variant, p.A179* (c.535C>T) that is predicted to produce a truncated TGFBI protein (Fig. 2A). The patient's father was also diagnosed as having GCD2 and had the p.R124H mutation but not the p.A179* variant, while her mother did not have an eye problem but refused TGFBI gene testing.


Mutation Analysis of the TGFBI Gene in Consecutive Korean Patients With Corneal Dystrophies.

Song JS, Lim DH, Chung ES, Chung TY, Ki CS - Ann Lab Med (2015)

Sequence electrophoerograms of novel TGFBI variants. (A) The c.535C>T (p.A179*) variant identified in a patient with granular corneal dystrophy type 2 (arrow). (B) The c.1706T>A (p.L569Q) variant identified in a patient with lattice corneal dystrophy, TGFBI type (arrow). (C) The c.1861A>C (p.T621P) variant identified in a patient with lattice corneal dystrophy, TGFBI type (arrow).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390702&req=5

Figure 2: Sequence electrophoerograms of novel TGFBI variants. (A) The c.535C>T (p.A179*) variant identified in a patient with granular corneal dystrophy type 2 (arrow). (B) The c.1706T>A (p.L569Q) variant identified in a patient with lattice corneal dystrophy, TGFBI type (arrow). (C) The c.1861A>C (p.T621P) variant identified in a patient with lattice corneal dystrophy, TGFBI type (arrow).
Mentions: Among the 74 patients clinically diagnosed as having GCD2, 73 (82.0%, 73/89) had the p.R124H mutation, while one patient had no mutations in the TGFBI gene (Fig. 1). One patient with the p.R124H mutation had an additional nonsense variant, p.A179* (c.535C>T) that is predicted to produce a truncated TGFBI protein (Fig. 2A). The patient's father was also diagnosed as having GCD2 and had the p.R124H mutation but not the p.A179* variant, while her mother did not have an eye problem but refused TGFBI gene testing.

Bottom Line: Of particular note, one patient with rapidly progressive CD had the p.R124H mutation as well as a novel nonsense variant with unknown clinical significance (p.A179*).This study provides epidemiological insight into CDs in a Korean population and reaffirms that GCD2 is the most common TGFBI CD phenotype and that p.R124H is the only mutation identified in patients with GCD2.In addition, we broaden the spectrum of TGFBI mutations by identifying two novel missense variants in patients with LCD1.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

ABSTRACT

Background: Mutations in the transforming growth factor β-induced gene (TGFBI) are major causes of genetic corneal dystrophies (CDs), which can be grouped into TGFBI CDs. Although a few studies have reported the clinical and genetic features of Korean patients with TGFBI CD, no data are available regarding the frequency and spectrum of TGFBI mutations in a consecutive series of Korean patients with clinically diagnosed CDs.

Methods: Patients with any type of CD, who underwent both ophthalmologic examination and TGFBI gene analysis by Sanger sequencing at a tertiary care hospital in Seoul, Korea from 2006 to 2013, were enrolled in this study.

Results: Among a total of 89 patients, 77 (86.5%) were diagnosed as having clinical TGFBI CD. Seventy-three out of 74 patients (98.6%) with granular CD type 2 (GCD2), had the p.R124H mutation. Of particular note, one patient with rapidly progressive CD had the p.R124H mutation as well as a novel nonsense variant with unknown clinical significance (p.A179*). In three patients with lattice CD type 1 (LCD1), one known mutation (p.R124C) and two novel variants (p.L569Q and p.T621P) in the TGFBI gene were identified.

Conclusions: This study provides epidemiological insight into CDs in a Korean population and reaffirms that GCD2 is the most common TGFBI CD phenotype and that p.R124H is the only mutation identified in patients with GCD2. In addition, we broaden the spectrum of TGFBI mutations by identifying two novel missense variants in patients with LCD1.

No MeSH data available.


Related in: MedlinePlus