Molecular Analysis of Plasma α1,3-Fucosyltransferase Deficiency and Development of the Methods for Its Genotyping

Abstract

Four patients with mental illness were found to be deficient in plasma α1,3-fucosyltransferase for the first time in Japan [Exp Clin Immunogenet 1999;16:125–130]. Complete sequencing of FUT6 genes in these individuals revealed the presence of two point mutations, i.e., G739 to A (Glu→247 to Lys) and C945 to A (Tyr→315 to stop). In addition to two reported alleles having G739 to A (pf1) and G739 to A and C945 to A (pf3), a new mutated allele having C945 to A (pf2) was found to be present and all the individuals who lack α1,3-fucosyltransferase activity in plasma were found to possess pf genes homozygously (pf/pf). In order to detect such lethal mutations in FUT6 genes easily, PCR-RFLP methods have also been developed and applied for the screening of FUT6 deficiency in a large number of samples which resulted in the demonstration of three additional FUT6-deficient individuals. The absence of α1,3-fucosylated molecules on α₁-acid glycoprotein in plasma from all the 7 individuals was confirmed to result from the plasma α1,3-fucosyltransferase deficiency.

Fucosylated Glycans in α1-Acid Glycoprotein for Monitoring Treatment Outcomes and Prognosis of Cancer Patients

“…The patient was, therefore, suggested to possess the lethal mutation of the FUT6 gene and to lack serum α1,3fucosyltransferase activity [ 38 ]. In fact, the patient was determined to possess the pf gene homozygously ( pf / pf ) indicating occurrence of lethal mutation in the FUT6 gens which resulted in the absence of fucosylated glycans in AGP [ 37 ]. However, a couple of fucosylated glycans were still detected as less than several % of the total glycans in AGP ( Fig 4b ).…”

“…Whereas, since all these glycans are synthesized enzymatically through catalytic actions of a series of glycosyltransferases, such enzymes could be an important target to detect glycan-based changes in malignancies involving possible establishment of a novel biomarker for diagnosis of cancer. In fact, our previous studies demonstrated the usefulness of analyzing α1,2- [ 47 – 49 ], α1,3- [ 20 , 21 , 37 , 38 , 50 – 54 ], α1,4- [ 55 – 58 ] and α1,6fucosyltransferase [ 59 ] activities using specific sugar-acceptors, which emphasized the specific role of the fucosylated antigens appeared to play on carcinogenesis [ 1 , 47 – 49 ]. In particular, significantly elevated activities of α1,3fucosyltransferase in plasma and/or serum have been observed in patients with diverse cancers [ 20 , 21 , 51 – 54 ].…”

“…Genomic DNA was extracted from peripheral blood samples by the standard phenol-chloroform extraction method. The FUT6 gene locus was PCR-amplified with ty-1 and ty-2 primers [ 37 ]. Nucleotide sequences of the PCR products were determined by a direct sequence using specific primers for the target.…”

Assessment of de novo copy-number variations in Italian patients with schizophrenia: Detection of putative mutations involving regulatory enhancer elements

“…Disruption of sphingolipid metabolism could result in widespread effects, related to diverse pathological deficits already described in schizophrenia, including myelination and oligodendrocyte function (Narayan et al 2009). Three fucosyltransferase genes (FUT3, FUT5 and FUT6) map in the duplicated region (Costache et al 1997), and plasma α1,3-fucosyltransferase deficiency was detected in Japanese patients with schizophrenia (Yazawa et al 1999;Tanaka et al 2001). Post-translational protein modifications can have a role in the pathophysiology of schizophrenia.…”

Transcriptional regulation of the fucosyltransferase VI gene in hepatocellular carcinoma cells

“…FUT VI is believed to contribute to sLeX synthesis in the liver or hepatocellular carcinoma HepG2 cells and to be involved in cancer metastasis [15][16][17]. Moreover, the level of α1,3-FUT activity in plasma is elevated in various cancerous conditions [18-α1,3-FUT activity and α1-3-fucosylation of serum glycoproteins [21].…”