Congenital disorder of glycosylation type Ij (CDG-Ij, DPAGT1-CDG): Extending the clinical and molecular spectrum of a rare disease

Autor: Gudrun Nürnberg, Thorsten Marquardt, Janine Reunert, C. Hertzberg, A.E. Würde, L. Lehle, Stephan Rust, S. Haverkämper, R. Rossi, Peter Nürnberg
Rok vydání: 2012
Předmět:
Adult
Lipopolysaccharides
congenital
hereditary
and neonatal diseases and abnormalities
Pathology
medicine.medical_specialty
Microcephaly
Glycosylation
Endocrinology
Diabetes and Metabolism
Molecular Sequence Data
Severe muscular hypotonia
Transferases (Other Substituted Phosphate Groups)
Biochemistry
chemistry.chemical_compound
Congenital Disorders of Glycosylation
Rare Diseases
Endocrinology
Genetics
medicine
Humans
Immunoprecipitation
Amino Acid Sequence
Molecular Biology
Cells
Cultured
Chromatography
High Pressure Liquid
Skin
chemistry.chemical_classification
Progressive microcephaly
Sequence Homology
Amino Acid
Muscular hypotonia
Homozygote
Infant
Newborn
DPAGT1
Fibroblasts
medicine.disease
chemistry
Mutation
Electrophoresis
Polyacrylamide Gel
Female
Glycoprotein
Congenital disorder of glycosylation
Zdroj: Molecular Genetics and Metabolism. 105:634-641
ISSN: 1096-7192
DOI: 10.1016/j.ymgme.2012.01.001
Popis: Congenital disorders of glycosylation (CDG) are caused by enzymatic defects of the formation or processing of lipid-linked oligosaccharides and glycoproteins. Since the majority of proteins is glycosylated, a defect in a singular CDG enzyme leads to a multisytemic disease with secondary malfunction of thousands of proteins. CDG-Ij (DPAGT1-CDG) is caused by a defect of the human DPAGT1 (UDP-GlcNAc: Dolichol Phosphate N-Acetylglucosamine-1-Phosphotransferase), catalyzing the first step of N-linked glycosylation. So far the clinical phenotype of only one CDG-Ij patient has been described. The patient showed severe muscular hypotonia, intractable seizures, developmental delay, mental retardation, microcephaly and exotropia. Molecular studies of this patient revealed the heterozygous mutation c.660A > G (Y170C; paternal) in combination with an uncharacterized splicing defect (maternal). Two further mutations, c.890A > T (I297F) and c.162-8 G > A as a splicing defect were detected when analyzing DPAGT1 in two affected siblings of a second family. We report two new patients with the novel homozygous mutation, c.341 C > G (A114G), causing a severe clinical phenotype, characterized by hyperexcitability, intractable seizures, bilateral cataracts, progressive microcephaly and muscular hypotonia. Both our patients died within their first year of life. With the discovery of this novel mutation and a detailed clinical description we extend the clinical features of CDG-Ij in order to improve early detection of this disease.
Databáze: OpenAIRE
Externí odkaz: