Novel mutations of CHST6 in Iranian patients with macular corneal dystrophy

[摘要] Purpose: To characterize mutationswithin the carbohydrate sulfotransferase 6 (CHST6) gene inIranian subjects from 12 families with macular corneal dystrophy (MCD).Methods: Genomic DNA was extracted fromperipheral blood of 20 affected patients and 60 healthy volunteersfollowed by polymerase chain reaction (PCR) and direct sequencing ofthe CHST6 coding region. The observed nucleotide sequences werethen compared with those found by investigators in other populationswith MCD and in the controls. Results: Analysis of CHST6revealed 11 different mutations. These mutations were comprised of sixnovel missense mutations (p.F55L, p.P132L, p.S136G, p.C149Y, p.D203Y,and p.H249R), one novel nonsense mutation (p.S48X), one novel frameshift (after P297), and three previously reported missense mutations(p.P31L, p.C165Y, and p.R127C). The majority of the detected MCDmutations are located in the binding sites or the binding pocket,except the p.P31L and p.H249R mutations. Conclusions: Nucleotide changes withinthe coding region of CHST6 are predicted to significantly alterthe encoded sulfotransferase within the evolutionary conservedsequences. Our findings show that CHST6 mutations areresponsible for the pathogenesis of MCD in Iranian patients. Moreover,the observation that some cases of MCD cannot be explained by mutationsin the coding region of CHST6 suggests that MCD may result frompossible upstream rearrangements in the CHST6 genomic region.

[学科分类] 生物化学/生物物理