However, screening of CHST6 in the proband demonstrated a novel homozygous missense mutation involving a highly conserved amino acid (c.518T > C; Leu173Pro) and undetectable serum AgKS levels in the proband confirmed the diagnosis of type I MCDC1.
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.
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.
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.
These findings fit the haplotype analysis that we reported previously and indicate that the predicted protein that is encoded by CHST6 is more severely affected in the individual with MCD type I than in the siblings with MCD type II.
These data demonstrate a high degree of allelic heterogeneity of the CHST6 gene in patient populations with MCD from Southern India, where this disease may have a relatively higher prevalence than in outbred communities.
CHST6 coding region analysis in 10 patients identified as having type I macular corneal dystrophy revealed 10 sequence changes: eight missense mutations, four of which are novel (Met104Val, Tyr110Cys, Gln122Pro, and Leu276Pro) and four of which have been reported previously (Ser51Leu, Pro72Ser, Cys102Gly, and Leu200Arg); one novel homozygous nonsense mutation in two patients from a single family (c. 1683C>T, Gln331X); and one frameshift mutation in a heterozygous state in a single patient (c.1744_1751dupGTGCGCTG).
A variety of previously unreported mutations in the coding region of the CHST6 gene are associated with type I MCD in a cohort of patients in southern India.
A variety of previously unreported mutations in the coding region of the CHST6 gene are associated with type I MCD in a cohort of patients in southern India.