Novel ALG8 mutations expand the clinical spectrum of congenital disorder of glycosylation type Ih

作者：Stoelting Torsten; Omran Heymut; Erlekotte Anne; Denecke Jonas; Reunert Janine; Marquardt Thorsten^*

来源：Molecular Genetics and Metabolism, 2009, 98(3): 305-309.

DOI：10.1016/j.ymgme.2009.06.010

• Congenital disorders of glycosylation
• CDG-Ih
• Inherited metabolic disease
• ALG8

Congenital disorders of glycosylation (CDG) are an expanding group of inherited disorders caused by defects in the N- or O-Glycosylation of proteins and lipids. Several CDG subtypes have been described so far, including CDG type Ih which is caused by a deficiency of the dolichyl-P-Glc:Glc(1)Man(9)GlcNAC(2)-PP-dolichyl alpha 1,3-glucosyltransferase (hALG8). The defect leads to an accumulation of Dol-PP-Glc-NAC(2)Man(9) and Dol-PP-GlcNAC(2)Man(9)Glc(1) in the endoplasmic reticulum of patients' fibroblasts that can be detected by analyzing the lipid-linked oligosaccharyl intermediates. Five patients with CDG-Ih have been described so far. The clinical presentation of four of these patients was severe with death in early infancy. In this report, we describe two mildly affected siblings with CDG-Ih caused by two novel mutations.
While one mutation (c.1434delC) causes a frame shift resulting in a premature termination codon (p.485X), the point mutation of the other allele (c.845C>T, p.A282V) causes an amino acid replacement in a highly conserved region of the hALG8 gene. The two siblings show similar symptoms, including pseudo-gynecomastia, epicanthus, muscular hypotonia, mental retardation and ataxia, expanding the genetic and clinical spectrum of CDG-Ih.

• 出版日期2009-11