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Clinical and molecular characterization of the first adult congenital disorder of glycosylation (CDG) type Ic patient

2005; Wiley; Volume: 137A; Issue: 1 Linguagem: Inglês

10.1002/ajmg.a.30831

1552-4833

Liangwu Sun, Erik A. Eklund, Johan L.K. Van Hove, Hudson H. Freeze, Janet A. Thomas,

Carbohydrate Chemistry and Synthesis

Abstract Congenital disorder of glycosylation (CDG) type Ic, the second largest subtype of CDG, is caused by mutations in human ALG6 (h ALG6 ). This gene encodes the α1,3‐glucosyltransferase that catalyzes transfer of the first glucose residue to the lipid‐linked oligosaccharide precursor for N‐linked glycosylation. In this report, we describe the first adult patient diagnosed with CDG‐Ic, carrying two previously unknown mutations. The first is a three base deletion (897‐899delAAT) leading to the loss of I299, the second is an intronic mutation (IVS7 + 2T > G) that causes aberrant splicing. Wildtype h ALG6 , delivered by a lentiviral vector into patient's fibroblasts, clearly improves the biochemical phenotype, which confirms that the mutations are disease‐causing. Striking clinical findings include limb deficiencies in the fingers, resembling brachydactyly type B, a deep vein thrombosis, pseudotumor cerebri, and endocrine disturbances with pronounced hyperandrogenism and virilization. However, even in adulthood, this patient shows normal magnetic resonance imaging of the brain. © 2005 Wiley‐Liss, Inc.