Posttranslationally glycosylated proteins are important in many biological processes in humans and Congenital disorders of glycosylation (CDGs) are associated with a broad range of phenotypes. Type I CDGs are a group of rare autosomal recessive conditions. To date 17 subtypes have been enzymatically and molecularly characterized. Impaired function of the enzyme dolichyl pyrophosphate Glc(1)Man(9)GlcNAc(2) alpha-1,3-glucosyltransferase encoded by the ALG8 gene, causes ALG8-CDG (CDG-Ih, OMIM #608104). This enzyme facilitates the transfer of a second glucose molecule to a growing lipid-linked oligosaccharide chain, a process that transpires in the endoplasmic reticulum (ER). We present a female patient of consanguineous parents, with pre- and postnatal growth retardation, dysmorphic features, significant developmental delay, visual impairment and an electrophoretic serum transferrin pattern indicative of a type I CDG. Type I CDG subgroup was determined by exome sequencing facilitated by homozygosity analysis. The patient was homozygous for two variants, nine nucleotides apart, in exon 8 of ALG8; c.799T > C [p.Ser267Pro] and c.808T > C [p.Phe270Leu]. Both missense mutations are predicted to affect a conserved region of an intraluminal ER loop of dolichyl pyrophosphate Glc(1)Man(9)GlcNAc(2) alpha-1,3-glucosyltransferase. To our knowledge, the current report describes the ninth published case of ALG8-CDG, contributing to the further delineation of this rare and variable disorder.
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