Meta-Biol

• Pathways

Phosphomannomutase 2 (PMM2) catalyses the isomerisation of mannose 6-phosphate (Man6P) to mannose 1-phosphate (Man1P) in the cytosol of cells. Man1P is a precursor in the synthesis of GDP-mannose and dolichol-phosphate-mannose, required for critical mannosyl transfer reactions in the N-glycosylation of proteins. Mutations in the PMM2 gene are one of the causes of Jaeken syndrome, a congenital disorder of glycosylation type 1a (PMM2-CDG, previously CDG-1a) (Matthijs et al. 1997). PMM2-CDG was first described in Belgian identical twin sisters, characterised by psychomotor retardation and multiple serum glycoprotein abnormalities. Serum and CSF transferrin were found to be deficient in sialic acid (Jaeken et al. 1984). The most common mutations with no detectable activity and causing a severe phenotype are R141H, D65Y, D188G, G117R and T237R (Matthijs et al. 1997, Matthijs et al. 1998, Kjaergaard et al. 1999, Vuillaumier-Barrot et al. 2000). The R141H mutation is never observed in the homozygous state. Mutations with residual activity producing a milder, less severe phenotype include F119L, C241S, C9Y, L32R and T226S (not annotated here; Vuillaumier-Barrot et al. 2000, Grunewald et al. 2001).