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Title: Mutations in the MGAT2 gene controlling complex N-glycan synthesis cause carbohydrate-deficient glycoprotein syndrome type II, an autosomal recessive disease with defective brain development

Carbohydrate-deficient glycoprotein syndrome (CDGS) type II is a multisystemic congenital disease with severe involvement of the nervous system. Two unrelated CDGS type II patients are shown to have point mutations (one patient having Ser{r_arrow}Phe and the other having His{r_arrow}Arg) in the catalytic domain of the gene MGAT2, encoding UDP-GlcNAc:{alpha}-6-D-mannoside {Beta}-1,2-N-ace-tylglucosaminyltransferase II (GnT II), an enzyme essential for biosynthesis of complex Asn-linked glycans. Both mutations caused both decreased expression of enzyme protein in a baculovirus/insect cell system and inactivation of enzyme activity. Restriction-endonuclease analysis of DNA from 23 blood relatives of one of these patients showed that 13 donors were heterozygotes; the other relatives and 21 unrelated donors were normal homozygotes. All heterozygotes showed a significant reduction (33%-68%) in mononuclear-cell GnT II activity. The data indicate that CDGS type II is an autosomal recessive disease and that complex Asn-linked glycans are essential for normal neurological development. 38 refs., 4 figs., 1 tab.
Authors:
; ;  [1]
  1. Univ. of Toronto (Canada) [and others
Publication Date:
OSTI Identifier:
476750
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Journal of Human Genetics; Journal Volume: 59; Journal Issue: 4; Other Information: PBD: Oct 1996
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; GENES; GENE MUTATIONS; GENE REGULATION; GENETIC MAPPING; BRAIN; ONTOGENESIS; ENZYMES; ENZYME ACTIVITY; PATIENTS; HEREDITARY DISEASES; METABOLIC DISEASES; CONGENITAL DISEASES; HUMAN CHROMOSOME 14; GLYCOPROTEINS; CARBOHYDRATES; RECESSIVE MUTATIONS; AMINO ACIDS; BIOSYNTHESIS; OLIGONUCLEOTIDES; POLYMERASE CHAIN REACTION