期刊
EUROPEAN JOURNAL OF HUMAN GENETICS
卷 21, 期 8, 页码 844-849出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ejhg.2012.257
关键词
exome sequencing; intellectual disability; DPAGT1; congenital disorders of glycosylation; iso-electric focusing; mass spectrometry
资金
- European Union [241995]
- Higher Education Commission (HEC), Islamabad, Pakistan
- NWO [40-00506-98-9001]
Congenital disorders of glycosylation (CDG) are a large group of recessive multisystem disorders caused by impaired protein or lipid glycosylation. The CDG-I subgroup is characterized by protein N-glycosylation defects originating in the endoplasmic reticulum. The genetic defect is known for 17 different CDG-I subtypes. Patients in the few reported DPAGT1-CDG families exhibit severe intellectual disability (ID), epilepsy, microcephaly, severe hypotonia, facial dysmorphism and structural brain anomalies. In this study, we report a non-consanguineous family with two affected adults presenting with a relatively mild phenotype consisting of moderate ID, epilepsy, hypotonia, aggressive behavior and balance problems. Exome sequencing revealed a compound heterozygous missense mutation, c.85A>T (p.I29F) and c.503T>C (p.L168P), in the DPAGT1 gene. The affected amino acids are located in the first and fifth transmembrane domains of the protein. Isoelectric focusing and high-resolution mass spectrometry analyses of serum transferrin revealed glycosylation profiles that are consistent with a CDG-I defect. Our results show that the clinical spectrum of DPAGT1-CDG is much broader than appreciated so far.
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