PMM2 intronic branch-site mutations in CDG-Ia.

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.