Identification of novel mutations of the CHST6 gene in Vietnamese families affected with macular corneal dystrophy in two generations.
OBJECTIVE
To report the clinical and genetic findings of Vietnamese families affected with macular corneal dystrophy (MCD) in 2 generations.


METHODS
Two families, including 7 patients and 3 unaffected members, were examined clinically. Blood samples were collected. Fifty normal Vietnamese individuals were used as controls. Genomic DNA was extracted from leukocytes. Analysis of the carbohydrate sulfotransferase (CHST6) gene was performed using polymerase chain reaction and direct sequencing.


RESULTS
The typical form of MCD was recognized in family B, in which sequencing of CHST6 gene revealed an nt 1067-1068ins(GGCCGTG) mutation (frameshift after 125V) homozygously in MCD patients and heterozygously in the unaffected members. Family N also showed clinical features of MCD, moderate in the mother but severe in the affected son. Sequencing revealed a single heterozygous Arg211Gln in the mother, compound heterozygous Arg211Gln+ Gln82Stop in the affected son, and heterozygous Arg211Gln mutation in the unaffected members. The identified mutations in these pedigrees were excluded from normal controls.


CONCLUSIONS
The novel frameshift and compound heterozygous mutations might be responsible for MCD in the families studied. The phenotypic variation between affected parents and offspring was unclear. In family N, severe MCD phenotype seen in the affected son may be due the fact that he had an early stop codon mutation (Gln82Stop).
Ha
Nguyen Thanh
NT
Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan. hant02@yahoo.com
Chau
Hoang Minh
HM
Cung
Le Xuan
le X
Thanh
Ton Kim
TK
Fujiki
Keiko
K
Murakami
Akira
A
Hiratsuka
Yoshimune
Y
Hasegawa
Nobuko
N
Kanai
Atsushi
A
D000293:Adolescent; D000328:Adult; D001120:Arginine; D001483:Base Sequence / Q000235:genetics; D016022:Case-Control Studies; D018388:Codon, Terminator; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology; D005260:Female; D016368:Frameshift Mutation; D005973:Glutamine; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D015238:Sulfotransferases / Q000235:genetics*; D014744:Vietnam; D000097811:Carbohydrate Sulfotransferases
D001120:Arginine; D018388:Codon, Terminator; D005973:Glutamine; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases