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

✍ Scribed by Liangwu Sun; Erik A. Eklund; Johan L.K. Van Hove; Hudson H. Freeze; Janet A. Thomas

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 178 KB
• Volume: 137A
• Category: Article
• ISSN: 1552-4825
• DOI: 10.1002/ajmg.a.30831

✦ Synopsis

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.