Peters'-plus syndrome is a congenital disorder of glycosylation caused by a defect in the beta1,3-glucosyltransferase that modifies thrombospondin type 1 repeats.
Genetic defects in glycosyltransferases are responsible for a number of developmental defects and diseases known as congenital disorders of glycosylation (CDGs). Peters'-plus syndrome, a rare autosomal recessive disorder, is now known to be a CDG. This syndrome is characterized by a specific malformation of the eye that includes corneal opaqueness and iridocorneal adhesions (Peters' anomaly). Affected individuals are short in stature and have short limbs, and may have cleft lip/palate, defects in the central nervous system, heart, and various other organs. The phenotype varies in severity, ranging from death in early childhood to a general delay in growth and development, and is often associated with mental retardation. The mutations responsible for Peters'-plus syndrome inactivate a beta1,3-glucosyltransferase whose function is to add a glucose moiety to O-linked fucose, forming a rare glucose-beta1,3-fucose disaccharide. This disaccharide modification is specific to thrombospondin type 1 repeats (TSRs), domains found in extracellular proteins that function in cell-cell and cell-matrix interactions and signalling. Some ninety human proteins contain TSRs, but thus far the disaccharide has been demonstrated on only thrombospondin 1, properdin, F-spondin, ADAMTS-13, and ADAMTSL-1. These proteins perform essential functions in embryonic development, tissue remodelling, angiogenesis, neurogenesis, and complement activation. Identification of the beta1,3-glucosyltransferase and its substrate proteins is a key step towards understanding their roles in human development, and to uncovering the molecular and cellular mechanisms underlying the clinical manifestations of Peters'-plus syndrome.
Heinonen
Taisto Y K
TY
Paediatric Research Centre, University of Tampere and Tampere University Hospital, Tampere, Finland.
Maki
Markku
M
D018981:Congenital Disorders of Glycosylation / Q000201:enzymology* / Q000235:genetics; D004187:Disaccharides / Q000096:biosynthesis / Q000235:genetics; D005124:Eye Abnormalities / Q000201:enzymology* / Q000235:genetics; D005700:Galactosyltransferases / Q000235:genetics / Q000378:metabolism*; D005964:Glucosyltransferases; D006031:Glycosylation; D006801:Humans; D009154:Mutation; D054730:Protein Interaction Domains and Motifs
D004187:Disaccharides; C514116:B3GLCT protein, human; D005700:Galactosyltransferases; D005964:Glucosyltransferases