In vitro expression of α-l-fucosidase activity polymorphism observed in plasma

Elsen, August F. Van; Leroy, Jules; Wauters, J.; Willems, Patrick J.; Buytaert, C.; Verheyen, K. L. P.

doi:10.1007/bf00279400

Cited by 17 publications

(3 citation statements)

References 11 publications

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“…23,24,26 Variants have also a lower fucosidase activity in cultured fibroblasts. 27 In leucocytes and lymphoblastoid cell lines, however, the fucosidase activity of variants and normals is not significantly different. 23,24 All eight FUCA1 exons and exon-intron boundaries from individuals who were homozygous for the low activity trait, were sequenced but no mutation was found (Seo and O'Brien, unpublished results).…”

Section: Low Plasma Activity Polymorphism In Fuca2mentioning

confidence: 95%

Spectrum of mutations in fucosidosis

et al. 1999

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Fucosidosis is a lysosomal storage disorder characterised by progressive psychomotor deterioration, angiokeratoma and growth retardation. It is due to deficient α-l-fucosidase activity leading to accumulation of fucose-containing glycolipids and glycoproteins in various tissues. Fucosidosis is extremely rare with less than 100 patients reported worldwide, although the disease occurs at a higher rate in Italy, in the Hispanic-American population of New Mexico and Colorado, and in Cuba. We present here a review study of the mutational spectrum of fucosidosis. Exon by exon mutation analysis of FUCA1, the structural gene of α-l-fucosidase, has identified the mutation(s) in nearly all fucosidosis patients investigated. The spectrum of the 22 mutations detected to date includes four missense mutations, 17 nonsense mutations consisting of seven stop codon mutations, six small deletions, two large deletions, one duplication, one small insertion and one splice site mutation. All these mutations lead to nearly absent enzymatic activity and severely reduced cross-reacting immunomaterial. The observed clinical variability is, therefore, not due to the nature of the fucosidosis mutation, but to secondary unknown factors.

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Section: Low Plasma Activity Polymorphism In Fuca2mentioning

confidence: 95%

Spectrum of mutations in fucosidosis

et al. 1999

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“…In human, there are two isoforms of AFUs, namely FUCA1 and FUCA2 that are predominantly localized in the tissues such as liver 11 , as well as plasma and fibroblasts 12 , respectively. FUCA1 is encoded by a gene on chromosome 1p (1p34) 13 and FUCA2 is encoded by a gene linked to plasminogen on chromosome 6 (6q24) 14 .…”

Section: The Structural Characteristics and Function Of Afusmentioning

confidence: 99%

Dual role of fucosidase in cancers and its clinical potential

Fu¹,

Guo²,

Feng³

et al. 2022

J. Cancer

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Glycosidases and glycosyltransferases greatly impact malignant phenotype of tumors though genetics and epigenetics mechanisms. As the member of glycoside hydrolase (GH) families 29A, α-L-fucosidases (AFUs) are involved in the hydrolysis of terminal L-fucose residues linked via α-1,2, α-1,3, α-1,4 or α-1,6 to the reducing end of N-acetyl glucosamine (GlcNAc) of oligosaccharide chains. The defucosylation process mediated by AFUs contributes to the development of various diseases, such as chronic inflammatory diseases, immune disorders, and autoimmune diseases by reducing the interaction between fucosylated adhesion molecules supporting leukocyte extravasation. AFUs also impair crucial cell-extracellular matrix (ECM) interactions and presumably subsequent cell signaling pathways, which lead to changes in tumor function and behavior. There are two isoforms of AFUs in human, namely α-L-fucosidase 1 (FUCA1) and α-L-fucosidase 2 (FUCA2), respectively. FUCA1 is a p53 target gene and can hydrolyze different fucosylation sites on epidermal growth factor receptor (EGFR), thereby determining the activation of EGFR. FUCA2 mediates the adhesion between Helicobacter pylori and gastric mucosa and is upregulated in 24 tumor types. Besides, based on the participation of AFU in signaling pathways and tumor progression, we discuss the prospect of AFU as a therapeutic target.

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“…The uptake of radiolabelled fucose into skin fibroblasts was normal.Studies of serum and teukocytes from clinically normal individuals have revealed an enzyme variant exhibiting low activity and increased lability (Ramage and Cunningham, 1975). A recent report (Van Elsen et al, 1983) has demonstrated that the specific features of the variant enzyme are expressed in variant fibroblasts. The reaction kinetics, pH optima and Km values are similar for variant and nonvariant fucosidases.…”

mentioning

confidence: 99%

Low fibroblast fucosidase activity: false‐positive diagnosis of fucosidosis in a patient with pseudohypoparathyroidism

Sewell

Gehler²,

Docktor³

1987

J of Inher Metab Disea

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Pseudohypoparathyroidism (McKusick 30080) is an inherited skeletal disorder due to a deficient end-organ response to endogenous parathyroid hormone (PTH). The patients are of stocky build, have short metacarpals/metatarsals, are usually mentally retarded, hypocalcaemic, hyperphosphataemic, have a raised serum PTH level and a defective urinary excretion of cAMP in response to PTH administration. Alpha fucosidase deficiency results in the storage disease fucosidosis (McKusick 23000) and may be subdivided into at least two forms dependant upon age of onset and severity of neurological involvement. There is an abnormal excretion of urinary fuco-oligosaccharides and keratan sulphate. This report describes low fibroblast fucosidase activity in a patient with pseudohypoparathyroidism.A 5-year-old boy was investigated on the basis of symptoms of psychomotor retardation. He was an obese child of normal height without facial coarsening or organomegaly. X-rays showed a macrocephalic skull, normal sella, hyperostosis of the frontal and occipital regions and short plump hands with coarse trabeculation. The metaphyses and epiphyses were normal. He was hypocalcaemic, hyperphosphataemic and had a raised PTH level. The results of a cAMP stimulation test were consistent with a diagnosis of pseudohypoparathyroidism.Urinary oligosaccharide and glycosaminoglycan excretion was normal. Serum and fibroblast a-fucosidase activity was around 10% of normal. The fibroblast enzyme showed a flattened pH profile with normal optima (pH 4.5 and pH 6.5). The apparent Km was normal. Heat inactivation at 51°C showed a pattern consistent with that of 'normal variant' patients (DiMatteo et al., 1976). The uptake of radiolabelled fucose into skin fibroblasts was normal.Studies of serum and teukocytes from clinically normal individuals have revealed an enzyme variant exhibiting low activity and increased lability (Ramage and Cunningham, 1975). A recent report (Van Elsen et al., 1983) has demonstrated that the specific features of the variant enzyme are expressed in variant fibroblasts. The reaction kinetics, pH optima and Km values are similar for variant and nonvariant fucosidases. The fibroblast variant enzyme has an activity of less than 50%. Our results agree with the above authors' in that a low a-fucosidase activity is expressed in variant fibroblasts. Our kinetic data did not differ from control values. However, the association of this variant with other clinical expressions has not been reported. Our tentative diagnosis of fucosidosis was attained before that of pseudohypoparathyroidism and although our patient exhibited none of the classical features of fucosidosis, the question of phenotypic variation must always be considered. Thus our case serves to illustrate a pitfall in the diagnosis of fucosidosis and 1Department of Paediatrics, Universit/its-Kinderklinik,

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In vitro expression of α-l-fucosidase activity polymorphism observed in plasma

Cited by 17 publications

References 11 publications

Spectrum of mutations in fucosidosis

Spectrum of mutations in fucosidosis

Dual role of fucosidase in cancers and its clinical potential

Low fibroblast fucosidase activity: false‐positive diagnosis of fucosidosis in a patient with pseudohypoparathyroidism

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