Novel mutation in the carbohydrate ulfotranferae gene (CHT6) in American patient with macular corneal dytrophy

Purpoe To further characterize the mutation within the CHT6 gene reponible for cauing macular corneal dytrophy in a cohort of affected patient from the United tate. Deign Experimental tudy. Method Genomic DNA wa extracted from buccal epithelium of 16 affected patient (14 familie), 17 unaffected relative, and 127 control, followed by polymerae chain reaction amplification and direct equencing of the CHT6 coding region. ubtyping of affected patient into type I and II macular corneal dytrophy wa performed by meauring antigenic keratan ulfate (AgK) erum level. Haplotype analyi wa performed in familie that demontrated common mutation. Reult CHT6 coding region analyi in 10 patient identified a having type I macular corneal dytrophy revealed 10 equence change: eight miene mutation, four of which are novel (Met104Val, Tyr110Cy, Gln122Pro, and Leu276Pro) and four of which have been reported previouly (er51Leu, Pro72er, Cy102Gly, and Leu200Arg); one novel homozygou nonene mutation in two patient from a ingle family (c. 1683C>T, Gln331X); and one framehift mutation in a heterozygou tate in a ingle patient (c.1744_1751dupGTGCGCTG). Mutation analyi in the four patient identified a having type II macular corneal dytrophy (erum ample were not obtained from two affected patient) revealed three patient heterozygou for either the c.923G>C, c.969C>A, or c.1519T>C equence change. The fourth patient wa compound heterozygou for c.969C>A and c.1291T>G. None of thee change wa oberved in 127 control individual. Haplotype analyi uing microatellite marker flanking the CHT6 gene did not reveal a common founder for the Leu200Arg (1291T>G) miene mutation, preent in five familie, identifying thi poition a a mutation hot-pot. Concluion A variety of previouly unreported mutation in the coding region of the CHT6 gene are aociated with type I macular corneal dytrophy in a cohort of patient from the United tate