title: Functional analysis of novel mutations in a congenital disorder of glycosylation Ia patient with mixed Asian ancestry.
abstract: Congenital disorders of glycosylation (CDG) are caused by autosomal recessive mutations in genes affecting N-glycan biosynthesis. Mutations in the PMM2 gene, which encodes the enzyme phosphomannomutase (mannose 6-phosphate <--> mannose 1-phosphate), give rise to the most common form: CDG-Ia. These patients typically present with dysmorphic features and neurological abnormalities, cerebellar hypoplasia, ataxia, hypotonia, and coagulopathy, in addition to feeding problems. However, the clinical symptoms vary greatly. The great majority of known CDG-Ia patients are of European descent where the most common mutant alleles originated. This ethnic bias can also be explained by lack of global awareness of the disorder. Here we report an Asian patient with prominent systemic features that we diagnosed with CDG-Ia resulting from two new mutations in the PMM2 gene (310C --> G resulting in L104V and an intronic mutation IVS1-1G --> A). The latter mutation seems to result in lower mRNA levels, and the L104V has been functionally analyzed in a yeast expression system together with known mutations. The Filipino and Cambodian origins of the parents show that CDG-Ia mutations occur in these ethnic groups as well as in Caucasians.
authors.affiliation: The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 9203 USA.
authors.forename: V
authors.initials: V
authors.lastname: Westphal
authors.forename: G M
authors.initials: GM
authors.lastname: Enns
authors.forename: M F
authors.initials: MF
authors.lastname: McCracken
authors.forename: H H
authors.initials: HH
authors.lastname: Freeze
mesh_terms: D000595:Amino Acid Sequence; D001213:Asian; D002160:Cambodia / Q000208:ethnology; D018981:Congenital Disorders of Glycosylation / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005192:Family Health; D005260:Female; D005816:Genetic Complementation Test; D006801:Humans; D007223:Infant; D009154:Mutation; D010679:Philippines / Q000208:ethnology; D017875:Phosphotransferases (Phosphomutases) / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development; D017386:Sequence Homology, Amino Acid
chemical_list: D018076:DNA, Complementary; D017875:Phosphotransferases (Phosphomutases); C052799:phosphomannomutase