title: PMM2 intronic branch-site mutations in CDG-Ia.
abstract: Congenital Disorders of Glycosylation (CDG, OMIM#212065)-Ia is an autosomal recessive disorder, characterized by central nervous system dysfunction and multiorgan failure associated with mutations in the PMM2 gene. We report two patients who are compound heterozygotes with respect to two new intronic mutations that affect a highly conserved adenosine in a consensus branch-site sequence. The mutations, one in intron 7: c.340 -23A > G (IVS7 -23A > G) and the other in intron 2: c.179 -25A > G (IVS2 -25A > G), are associated with the c.422G > A (R141H) and c.193 G > T (D65Y) mutations, respectively. The c.179 -25A > G and the c.340 -23A > G changes cause exon 3 and exon 8 to be lost at the RNA level, respectively. This kind of mutation can cause a problem in molecular diagnosis of CDG-Ia if intronic primers are not correctly chosen, and if molecular diagnosis is not performed at both the DNA and mRNA levels.
authors.affiliation: Biochimie A, Hôpital Bichat-Claude Bernard, AP-HP, Paris, France. sandrne.vuillaumier@bch.ap-hop-paris.fr
authors.forename: Sandrine
authors.initials: S
authors.lastname: Vuillaumier-Barrot
authors.forename: Christiane
authors.initials: C
authors.lastname: Le Bizec
authors.forename: Pascale
authors.initials: P
authors.lastname: De Lonlay
authors.forename: Nathalie
authors.initials: N
authors.lastname: Madinier-Chappat
authors.forename: Anne
authors.initials: A
authors.lastname: Barnier
authors.forename: Thierry
authors.initials: T
authors.lastname: Dupré
authors.forename: Geneviève
authors.initials: G
authors.lastname: Durand
authors.forename: Nathalie
authors.initials: N
authors.lastname: Seta
mesh_terms: D001483:Base Sequence; D018981:Congenital Disorders of Glycosylation / Q000235:genetics*; D016384:Consensus Sequence; D006031:Glycosylation; D006579:Heterozygote; D006801:Humans; D007438:Introns; D008297:Male; D009154:Mutation; D017875:Phosphotransferases (Phosphomutases) / Q000172:deficiency* / Q000235:genetics*; D012326:RNA Splicing
chemical_list: D017875:Phosphotransferases (Phosphomutases); C052799:phosphomannomutase