Identification of four novel PMM2 mutations in congenital disorders of glycosylation (CDG) Ia French patients

We screened 11 unrelated French patients with congenital disorders of glyco sylation (CDG) Ia for PMM2 mutations. Twenty one missense mutations on the 22 chromosomes (95%) including four novel mutations were identified: C9Y (G 26A) in exon 1, L32R (TA95GC) in exon 2, and T226S (C677G) and C241S (G722C ) in exon 8. We studied the PMM activity of these four novel mutant protein s and of the R141H mutant protein in an E coli expression system. The T226S , C9Y, L32R, and C241S mutant proteins have decreased specific activity (23 to 41% of normal), are all more or less thermolabile, and R141H has no det ectable activity. Our results indicate that the new mutations identified he re are less severe than the inactive R141H mutant protein, conferring resid ual PMM activity compatible with life.