OBJECTIVE: To further characterize the role of the carbohydrate sulfotransferase (CHST6) gene in macular corneal dystrophy (MCD) through identification of causative mutations in a cohort of affected patients from southern India. METHODS: Genomic DNA was extracted from buccal epithelium of 75 patients (51 families) with MCD, 33 unaffected relatives, and 48 healthy volunteers. The coding region of the CHST6 gene was evaluated by means of polymerase chain reaction amplification and direct sequencing. Subtyping of MCD into types I and II was performed by measuring serum levels of antigenic keratan sulfate. RESULTS: Seventy patients were classified as having type I MCD, and 5 patients as having type II MCD. Analysis of the CHST6 coding region in patients with type I MCD identified 11 homozygous missense mutations (Leu22Arg, His42Tyr, Arg50Cys, Arg50Leu, Ser53Leu, Arg97Pro, Cys102Tyr, Arg127Cys, Arg205Gln, His249Pro, and Glu274Lys), 2 compound heterozygous missense mutations (Arg93His and Ala206Thr), 5 homozygous deletion mutations (delCG707-708, delC890, delA1237, del1748-1770, and delORF), and 2 homozygous replacement mutations (ACCTAC 1273 GGT, and GCG 1304 AT). One patient with type II MCD was heterozygous for the C890 deletion mutation, whereas 4 possessed no CHST6 coding region mutations. CONCLUSION: 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. CLINICAL RELEVANCE: An improved understanding of the genetic basis of MCD allows for earlier, more accurate diagnosis of affected individuals, and may provide the foundation for the development of novel disease treatments.
OBJECTIVE: To further characterize the role of the carbohydrate sulfotransferase (CHST6) gene in macular corneal dystrophy (MCD) through identification of causative mutations in a cohort of affected patients from southern India. METHODS: Genomic DNA was extracted from buccal epithelium of 75 patients (51 families) with MCD, 33 unaffected relatives, and 48 healthy volunteers. The coding region of the CHST6 gene was evaluated by means of polymerase chain reaction amplification and direct sequencing. Subtyping of MCD into types I and II was performed by measuring serum levels of antigenic keratan sulfate. RESULTS: Seventy patients were classified as having type I MCD, and 5 patients as having type II MCD. Analysis of the CHST6 coding region in patients with type I MCD identified 11 homozygous missense mutations (Leu22Arg, His42Tyr, Arg50Cys, Arg50Leu, Ser53Leu, Arg97Pro, Cys102Tyr, Arg127Cys, Arg205Gln, His249Pro, and Glu274Lys), 2 compound heterozygous missense mutations (Arg93His and Ala206Thr), 5 homozygous deletion mutations (delCG707-708, delC890, delA1237, del1748-1770, and delORF), and 2 homozygous replacement mutations (ACCTAC 1273 GGT, and GCG 1304 AT). One patient with type II MCD was heterozygous for the C890 deletion mutation, whereas 4 possessed no CHST6 coding region mutations. CONCLUSION: 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. CLINICAL RELEVANCE: An improved understanding of the genetic basis of MCD allows for earlier, more accurate diagnosis of affected individuals, and may provide the foundation for the development of novel disease treatments.
Authors: Jayne S Weiss; H U Møller; Walter Lisch; Shigeru Kinoshita; Anthony J Aldave; Michael W Belin; Tero Kivelä; Massimo Busin; Francis L Munier; Berthold Seitz; John Sutphin; Cecilie Bredrup; Mark J Mannis; Christopher J Rapuano; Gabriel Van Rij; Eung Kweon Kim; Gordon K Klintworth Journal: Cornea Date: 2008-12 Impact factor: 2.651
Authors: Robert D Young; Tomoya O Akama; Petra Liskova; Neil D Ebenezer; Bruce Allan; Briedgeen Kerr; Bruce Caterson; Michiko N Fukuda; Andrew J Quantock Journal: Histochem Cell Biol Date: 2006-08-30 Impact factor: 4.304
Authors: Afia Sultana; Gordon K Klintworth; Eugene J-M A Thonar; Geeta K Vemuganti; Chitra Kannabiran Journal: Mol Vis Date: 2009-02-09 Impact factor: 2.367
Authors: Yasutaka Hayashida; Tomoya O Akama; Nicola Beecher; Philip Lewis; Robert D Young; Keith M Meek; Briedgeen Kerr; Clare E Hughes; Bruce Caterson; Akira Tanigami; Jun Nakayama; Michiko N Fukada; Yasuo Tano; Kohji Nishida; Andrew J Quantock Journal: Proc Natl Acad Sci U S A Date: 2006-08-25 Impact factor: 11.205