A mutation in the human MPDU1 gene causes congenital disorder of glycosylation type If (CDG-If).
We describe a new congenital disorder of glycosylation, CDG-If. The patient has severe psychomotor retardation, seizures, failure to thrive, dry skin and scaling with erythroderma, and impaired vision. CDG-If is caused by a defect in the gene MPDU1, the human homologue of hamster Lec35, and is the first disorder to affect the use, rather than the biosynthesis, of donor substrates for lipid-linked oligosaccharides. This leads to the synthesis of incomplete and poorly transferred precursor oligosaccharides lacking both mannose and glucose residues. The patient has a homozygous point mutation (221T-->C, L74S) in a semiconserved amino acid of MPDU1. Chinese hamster ovary Lec35 cells lack a functional Lec35 gene and synthesize truncated lipid-linked oligosaccharides similar to the patient's. They lack glucose and mannose residues donated by Glc-P-Dol and Man-P-Dol. Transfection with the normal human MPDU1 allele nearly completely restores normal glycosylation, whereas transfection with the patient's MPDU1 allele only weakly restores normal glycosylation. This work provides a new clinical picture for another CDG that may involve synthesis of multiple types of glycoconjugates.
Kranz
C
C
Klinik und Poliklinik für Kinderheilkunde, Münster, Germany.
Denecke
J
J
Lehrman
M A
MA
Ray
S
S
Kienz
P
P
Kreissel
G
G
Sagi
D
D
Peter-Katalinic
J
J
Freeze
H H
HH
Schmid
T
T
Jackowski-Dohrmann
S
S
Harms
E
E
Marquardt
T
T
D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D001797:Blood Protein Electrophoresis; D016466:CHO Cells; D018981:Congenital Disorders of Glycosylation / Q000235:genetics*; D006224:Cricetinae; D006031:Glycosylation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009844:Oligosaccharides / Q000032:analysis; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics*
C100352:Lec35 protein, Cricetulus griseus; D009844:Oligosaccharides; D012097:Repressor Proteins