TY - JOUR
T1 - Transferrin mutations at the glycosylation site complicate diagnosis of congenital disorders of glycosylation type i
AU - Guillard, Mailys
AU - Wada, Yoshinao
AU - Hansikova, Hana
AU - Yuasa, Isao
AU - Vesela, Katerina
AU - Ondruskova, Nina
AU - Kadoya, MacHiko
AU - Janssen, Alice
AU - Van Den Heuvel, Lambertus P.W.J.
AU - Morava, Eva
AU - Zeman, Jiri
AU - Wevers, Ron A.
AU - Lefeber, Dirk J.
N1 - Funding Information:
Acknowledgement This work was supported by the European Commission (LSHM-CT2005-512131, Euroglycanet) and Metakids and a grant from the Ministry of Education, Youth and Sports of the Czech Republic MSM 0021620806.
PY - 2011/8
Y1 - 2011/8
N2 - Congenital disorders of glycosylation (CDG) form a group of metabolic disorders caused by deficient glycosylation of proteins and/or lipids. Isoelectric focusing (IEF) of serum transferrin is the most common screening method to detect abnormalities of protein N-glycosylation. On the basis of the IEF profile, patients can be grouped into CDG type I or CDG type II. Several protein variants of transferrin are known that result in a shift in isoelectric point (pI). In some cases, these protein variants co-migrate with transferrin glycoforms, which complicates interpretation. In two patients with abnormal serum transferrin IEF profiles, neuraminidase digestion and subsequent IEF showed profiles suggestive of the diagnosis of CDG type I. Mass spectrometry of tryptic peptides of immunopurified transferrin, however, revealed a novel mutation at the N-glycan attachment site. In case 1, a peptide with mutation p.Asn630Thr in the 2nd glycosylation site was identified, resulting in an additional band at disialotransferrin position on IEF. After neuraminidase digestion, a single band was found at the asialotransferrin position, indistinguishable from CDG type I patients. In case 2, a peptide with mutation p.Asn432His was found. These results show the use of mass spectrometry of transferrin peptides in the diagnostic track of CDG type I.
AB - Congenital disorders of glycosylation (CDG) form a group of metabolic disorders caused by deficient glycosylation of proteins and/or lipids. Isoelectric focusing (IEF) of serum transferrin is the most common screening method to detect abnormalities of protein N-glycosylation. On the basis of the IEF profile, patients can be grouped into CDG type I or CDG type II. Several protein variants of transferrin are known that result in a shift in isoelectric point (pI). In some cases, these protein variants co-migrate with transferrin glycoforms, which complicates interpretation. In two patients with abnormal serum transferrin IEF profiles, neuraminidase digestion and subsequent IEF showed profiles suggestive of the diagnosis of CDG type I. Mass spectrometry of tryptic peptides of immunopurified transferrin, however, revealed a novel mutation at the N-glycan attachment site. In case 1, a peptide with mutation p.Asn630Thr in the 2nd glycosylation site was identified, resulting in an additional band at disialotransferrin position on IEF. After neuraminidase digestion, a single band was found at the asialotransferrin position, indistinguishable from CDG type I patients. In case 2, a peptide with mutation p.Asn432His was found. These results show the use of mass spectrometry of transferrin peptides in the diagnostic track of CDG type I.
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U2 - 10.1007/s10545-011-9311-y
DO - 10.1007/s10545-011-9311-y
M3 - Article
C2 - 21431619
AN - SCOPUS:79961168906
SN - 0141-8955
VL - 34
SP - 901
EP - 906
JO - Journal of inherited metabolic disease
JF - Journal of inherited metabolic disease
IS - 4
ER -