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Clinical and molecular characterization of the first adult congenital disorder of glycosylation (CDG) type Ic patient
Author(s) -
Sun Liangwu,
Eklund Erik A.,
Van Hove Johan L.K.,
Freeze Hudson H.,
Thomas Janet A.
Publication year - 2005
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.30831
Subject(s) - glycosylation , exon , brachydactyly , compound heterozygosity , phenotype , biology , mutation , point mutation , genetics , medicine , gene , endocrinology , short stature
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.