CHST6 mutations in North American subjects with macular corneal dystrophy: a comprehensive molecular genetic review.
OBJECTIVE
To evaluate mutations in the carbohydrate sulfotransferase-6 (CHST6) gene in American subjects with macular corneal dystrophy (MCD).


METHODS
We analyzed CHST6 in 57 patients from 31 families with MCD from the United States, 57 carriers (parents or children), and 27 unaffected blood relatives of affected subjects. We compared the observed nucleotide sequences with those found by numerous investigators in other populations with MCD and in controls.


RESULTS
In 24 families, the corneal disorder could be explained by mutations in the coding region of CHST6 or in the region upstream of this gene in both the maternal and paternal chromosome. In most instances of MCD a homozygous or heterozygous missense mutation in exon 3 of CHST6 was found. Six cases resulted from a deletion upstream of CHST6.


CONCLUSIONS
Nucleotide changes within the coding region of CHST6 are predicted to alter the encoded protein significantly within evolutionary conserved parts of the encoded sulfotransferase. Our findings support the hypothesis that CHST6 mutations are cardinal to the pathogenesis of MCD. Moreover, the observation that some cases of MCD cannot be explained by mutations in CHST6 suggests that MCD may result from other subtle changes in CHST6 or from genetic heterogeneity.
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. Klint001@mc.duke.edu
Gordon K
GK
Klintworth
Clayton F
CF
Smith
Brandy L
BL
Bowling
D020121:5' Untranslated Regions / Q000235:genetics; D002875:Chromosomes; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D004251:DNA Transposable Elements; D005220:Fathers; D016368:Frameshift Mutation; D017353:Gene Deletion; D006801:Humans; D008967:Molecular Biology / Q000379:methods; D009035:Mothers; D009154:Mutation; D009656:North America; D020641:Polymorphism, Single Nucleotide; D015238:Sulfotransferases / Q000235:genetics*; D000097811:Carbohydrate Sulfotransferases
D020121:5' Untranslated Regions; D004251:DNA Transposable Elements; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases