Genetic analysis ofCHST6andTGFBIin Turkish patients with corneal dystrophies: Five novel variations inCHST6.
To identify pathogenic variations incarbohydrate sulfotransferase 6(CHST6) andtransforming growth factor, beta-induced(TGFBI) genes in Turkish patients with corneal dystrophy (CD).



In this study, patients with macular corneal dystrophy (MCD; n = 18), granular corneal dystrophy type 1 (GCD1; n = 12), and lattice corneal dystrophy type 1 (LCD1; n = 4), as well as 50 healthy controls, were subjected to clinical and genetic examinations. The level of antigenic keratan sulfate (AgKS) in the serum samples of patients with MCD was determined with enzyme-linked immunosorbent assay (ELISA) to immunophenotypically subtype the patients as MCD type I and MCD type II. DNA was isolated from venous blood samples from the patients and controls. Variations were analyzed with DNA sequencing in the coding region ofCHST6in patients with MCD and exons 4 and 12 inTGFBIin patients with LCD1 and GCD1. Clinical characteristics and the detected variations were evaluated to determine any existing genotype-phenotype correlations.



The previously reported R555W mutation inTGFBIwas detected in 12 patients with GCD1, and the R124C mutation inTGFBIwas detected in four patients with LCD1. Serum AgKS levels indicated that 12 patients with MCD were in subgroup I, and five patients with MCD were in subgroup II. No genetic variation was detected in the coding region ofCHST6for three patients with MCD type II. In other patients with MCD, three previously reported missense variations (c. 1A>T, c.738C>G, and c.631 C>T), three novel missense variations (c.164 T>C, c.526 G>A, c. 610 C>T), and two novel frameshift variations (c.894_895 insG and c. 462_463 delGC) were detected. These variations did not exist in the control chromosomes, 1000 Genomes, and dbSNP.



This is the first molecular analysis ofTGFBIandCHST6in Turkish patients with different types of CD. We detected previously reported, well-known hot spot mutations inTGFBIin the patients with GCD1 and LCD1. Eight likely pathogenic variations inCHST6, five of them novel, were reported in patients with MCD, which enlarges the mutational spectrum of MCD.
Polatlı Duatepe State Hospital, Ophthalmology Department, Ankara. Turkey; Hacettepe Faculty of Medicine, Medical Biology Department, Ankara, Turkey.
Fulya
F
Yaylacioglu Tuncay
Hacettepe Faculty of Medicine, Medical Biology Department, Ankara, Turkey.
Gülsüm
G
Kayman Kurekci
Gazi Faculty of Medicine, Medical Genetics Department, Ankara, Turkey.
Sezen
S
Guntekin Ergun
Gazi Faculty of Medicine, Biochemistry Department, Ankara, Turkey.
Ozge Tugce
OT
Pasaoglu
Gazi Faculty of Medicine, Ophthalmology Department, Ankara, Turkey.
Rustu Fikret
RF
Akata
Hacettepe Faculty of Medicine, Medical Biology Department, Ankara, Turkey.
Pervin Rukiye
PR
Dincer
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics; D003317:Corneal Dystrophies, Hereditary / Q000097:blood / Q000235:genetics*; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007633:Keratins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016415:Sequence Alignment; D013431:Sulfates / Q000097:blood; D015238:Sulfotransferases / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014421:Turkey; D055815:Young Adult; D000097811:Carbohydrate Sulfotransferases; D000099222:betaIG-H3 Protein
D016326:Extracellular Matrix Proteins; D007633:Keratins; D013431:Sulfates; D015238:Sulfotransferases; D016212:Transforming Growth Factor beta; D000097811:Carbohydrate Sulfotransferases; D000099222:betaIG-H3 Protein