PMM2-CDG: Phenotype and genotype in four affected family members

• Here we report on a large Italian PMM2-CDG family.
• We have identified four affected members and three mutations.
• The 2 older patients have a mutation association which has not been reported before.
• The most severely affected member had in addition an ALG6 mutation.
• The clinical picture of the 2 old patients highlights the disease natural history.

Congenital disorders of glycosylation (CDG) are genetic defects in protein and lipid glycosylation. PMM2-CDG is the most prevalent protein N-glycosylation disorder with more than 700 reported patients. Here we report on a large Italian family with four affected members and three mutations. Two young sisters are compound heterozygous for mutations p.Leu32Arg and p.Arg141His, while two paternal great-aunts are compound heterozygosity for p.Leu32Arg and p.Thr237Met. The latter association has not been reported before. The most severely affected member had in addition an ALG6 mutation known to exacerbate the phenotype of patients with PMM2-CDG.