title: Congenital disorder of glycosylation Ic in patients of Indian origin.
abstract: Congenital disorder of glycosylation type Ic (CDG-Ic) is caused by mutations in ALG6, encoding an alpha 1,3-glucosyltransferase. The most frequent mutation found in this gene (C998T resulting in an A333V substitution) has until now been found only in patients of European origin. Here we describe the first occurrence of this CDG-Ic mutation in patients of Indian origin. Of three Indian patients described in this study, patient 1 was homozygous and patient 2 heterozygous for the A333V mutation. In patient 2 we also found a new mutation, IVS3+2_3insT, just 3bp away from the previously described IVS3+5G>A substitution; both mutations resulted in exon 3 skipping. We screened a panel of >350 genomic DNA samples from an ethnically diverse American population to determine the frequency of the A333V mutation. None of the samples carried this mutation, indicating the frequency of patients carrying this homozygous mutation should be <1 in 5x10(5). The discovery of the common CDG-Ic mutation A333V in an Indian population raises questions as to its ethnic origin.
authors.affiliation: The Burnham Institute, Glycobiology and Carbohydrate Chemistry Program, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Newell
authors.forename: N-S
authors.initials: NS
authors.lastname: Seo
authors.forename: G M
authors.initials: GM
authors.lastname: Enns
authors.forename: M
authors.initials: M
authors.lastname: McCraken
authors.forename: J F
authors.initials: JF
authors.lastname: Mantovani
authors.forename: H H
authors.initials: HH
authors.lastname: Freeze
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D018929:Cell Culture Techniques; D018981:Congenital Disorders of Glycosylation / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D014644:Genetic Variation; D005964:Glucosyltransferases / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000302:isolation & purification
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; C498467:ALG6 protein, human; D005964:Glucosyltransferases; C119841:dolichyl pyrophosphate Man(9)GlcNAc(2) alpha1,3-glucosyltransferase