Novel Mutations in the CHST6 Gene Associated With Macular Corneal Dystrophy in Southern India

Abstract

To further characterize the role of the carbohydrate sulfotransferase (CHST6) gene in macular corneal dystrophy (MCD) through identification of causative mutations in a cohort of affected patients from southern India. Methods: Genomic DNA was extracted from buccal epithelium of 75 patients (51 families) with MCD, 33 unaffected relatives, and 48 healthy volunteers. The coding region of the CHST6 gene was evaluated by means of polymerase chain reaction amplification and direct sequencing. Subtyping of MCD into types I and II was performed by measuring serum levels of antigenic keratan sulfate. Results: Seventy patients were classified as having type I MCD, and 5 patients as having type II MCD. Analysis of the CHST6 coding region in patients with type I MCD identified 11 homozygous missense mutations (Leu22Arg,

Genetic Analysis of CHST6 Gene in Indian Families with Macular Corneal Dystrophy

“…The identified known mutations have been observed among patients from several populations included India Saudi Arabia, Korea, Egypt, Japan, America and France [2,3,1517,18,23]. This additionally supports our findings showed a high degree of mutational heterogeneity among the patients studied.…”

“…Additionally, we have also observed a hotspot missense mutation (S53L) in 10 patients from different MCD families that leads to unstable protein (instability index 45.10) this mutation was already reported in 7 patients from seven South Indian families and the same mutation was identified in an American population suggesting a hotspot mutation [2,12,19]. Previous studies suggested that this mutation might be present in the 3'-phosphate-binding domain of C-GlcNac-6-ST enzyme.…”

“…Interestingly, we have identified 6 novel mutations in six MCD patients and 11 different known mutations in 38 patients. Previous studies have shown in Saudi Arabian and South Indian population that the prevalence of MCD is high; most probably due to the higher frequency of consanguineous marriage in these ethnic population [2,3]. In our current study, out of 55 families studied, we have also analysed 30 south Indian families with consanguineous marriage.…”

“…It was first described by Groenouw in 1890. Due to high degree of consanguinity in some ethnic population, this disorder is highly prevalent in Saudi Arabia and South Indian population [2,3]. The Clinical manifestations of MCD usually occurs by irregular, focal haze formation that leads to greywhite opacities eventually leading to decreased visual acuity by the fifth decade of life [4].…”

“…The recurrence rate of corneal opacities is more than 40% in macular corneal grafts even after 10 years of Penetrating Keratoplasty (PKP) [7]. CHST6 gene is the only candidate gene so far known in MCD and has been further screened in different ethnic populations across the world [2,3,[8][9][10][11][12][13][14][15][16][17]. It is located on chromosome 16q22 [18,19].…”