CHST6 mutations in North American subjects with macularcorneal dystrophy: a comprehensive molecular genetic review

[摘要] Purpose: To evaluate mutations in the carbohydratesulfotransferase-6 (CHST6) gene in American subjects with macularcorneal dystrophy (MCD).Methods: We analyzed CHST6 in 57 patients from 31 families withMCD from the United States, 57 carriers (parents or children), and 27unaffected blood relatives of affected subjects. We compared theobserved nucleotide sequences with those found by numerous investigatorsin other populations with MCD and in controls.Results: In 24 families, the corneal disorder could be explained bymutations in the coding region of CHST6 or in the region upstream ofthis gene in both the maternal and paternal chromosome. In mostinstances of MCD a homozygous or heterozygous missense mutation in exon3 of CHST6 was found. Six cases resulted from a deletion upstream ofCHST6.Conclusions: Nucleotide changes within the coding region ofCHST6 are predicted to alter the encoded protein significantlywithin evolutionary conserved parts of the encoded sulfotransferase. Ourfindings support the hypothesis that CHST6 mutations are cardinal tothe pathogenesis of MCD. Moreover, the observation that some cases ofMCD cannot be explained by mutations in CHST6 suggests that MCD mayresult from other subtle changes in CHST6 or from geneticheterogeneity.

[学科分类] 生物化学/生物物理