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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

Slit-lamp photographs. (A) Patient with GCD2 without any TGFBI mutations and a few discrete granular deposits in the anterior stroma with unilateral manifestation. (B) Patient with GCD2 carrying a novel p.A179* variant, as well as the p.R124H mutation, with progressed granular opacities in a dense confluent pattern covering most of the corneal surface. (C) Patient with LCD1, carrying the p.L569Q variant and large lattice lines. (D) Patient with LCD1, carrying the p.T621P variant with recurrent corneal erosions with typical lattice lines.
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Figure 3: Slit-lamp photographs. (A) Patient with GCD2 without any TGFBI mutations and a few discrete granular deposits in the anterior stroma with unilateral manifestation. (B) Patient with GCD2 carrying a novel p.A179* variant, as well as the p.R124H mutation, with progressed granular opacities in a dense confluent pattern covering most of the corneal surface. (C) Patient with LCD1, carrying the p.L569Q variant and large lattice lines. (D) Patient with LCD1, carrying the p.T621P variant with recurrent corneal erosions with typical lattice lines.

Mentions: The patient with GCD2 who lacked any mutations in the TGFBI gene was a young 26-yr-old woman who showed a few discrete granular deposits in the anterior stroma with unilateral manifestation (Fig. 3A). Although fine, discrete round opacities in the anterior stroma are indicative of early GCD2 symptoms, unilateral manifestation is somewhat atypical [14]. Because the patient refused to provide information regarding her family history, we could not determine whether this condition was inherited or not.


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)

Slit-lamp photographs. (A) Patient with GCD2 without any TGFBI mutations and a few discrete granular deposits in the anterior stroma with unilateral manifestation. (B) Patient with GCD2 carrying a novel p.A179* variant, as well as the p.R124H mutation, with progressed granular opacities in a dense confluent pattern covering most of the corneal surface. (C) Patient with LCD1, carrying the p.L569Q variant and large lattice lines. (D) Patient with LCD1, carrying the p.T621P variant with recurrent corneal erosions with typical lattice lines.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Slit-lamp photographs. (A) Patient with GCD2 without any TGFBI mutations and a few discrete granular deposits in the anterior stroma with unilateral manifestation. (B) Patient with GCD2 carrying a novel p.A179* variant, as well as the p.R124H mutation, with progressed granular opacities in a dense confluent pattern covering most of the corneal surface. (C) Patient with LCD1, carrying the p.L569Q variant and large lattice lines. (D) Patient with LCD1, carrying the p.T621P variant with recurrent corneal erosions with typical lattice lines.
Mentions: The patient with GCD2 who lacked any mutations in the TGFBI gene was a young 26-yr-old woman who showed a few discrete granular deposits in the anterior stroma with unilateral manifestation (Fig. 3A). Although fine, discrete round opacities in the anterior stroma are indicative of early GCD2 symptoms, unilateral manifestation is somewhat atypical [14]. Because the patient refused to provide information regarding her family history, we could not determine whether this condition was inherited or not.

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