Fabry's Disease: Antenatal Detection

Brady, Roscoe O.; Uhlendorf, B. William; Jacobson, Cecil B.

doi:10.1126/science.172.3979.174

Cited by 117 publications

(23 citation statements)

References 8 publications

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“…Successful diagnostic procedures based on quantitative enzyme assays have been carried out on cultured fibroblasts and on cells from a fetus at risk [51], and an unusual case of Fabry's disease, with mild manifesta tions of the disease and both A and B forms of the enzyme present in fi broblast cultures, has also been reported [52].…”

Section: A-galactosidasementioning

confidence: 99%

Multiple Forms of Glycosidases in the Normal and Pathological States

Robinson¹

1974

Enzyme

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Multiple forms of α- and β-galactosidase, α- and β-glucosidase, α- and β-hexosaminidases, α-mannosidase, α-fucosidase, and α-iduronidase of human tissues are surveyed. Their relationship to known storage disorders of glycolipid, glycoprotein, and mucopolysaccharide metabolism are discussed. A sub-unit hypothesis is presented to explain the interrelationships of multiple forms of β-N-acetylhexosaminidases that may be of wider application to include other glycosidases.

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Section: A-galactosidasementioning

confidence: 99%

Multiple Forms of Glycosidases in the Normal and Pathological States

Robinson¹

1974

Enzyme

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“…Prenatal diagnosis of at-risk male fetuses can be made reliably by demonstration of the enzymatic defect in fetal cells obtained by amniocentesis or chorionic villi sampling (e.g., 7,8). In contrast, enzymatic identification of female carriers of the Fabry gene is less reliable inasmuch as heterozygotes can express levels of a-galactosidase activity ranging from essentially zero to normal owing to random X-chromosomal inactivation (9,10).…”

Section: Introductionmentioning

confidence: 99%

Fabry disease: six gene rearrangements and an exonic point mutation in the alpha-galactosidase gene.

Bernstein¹,

Bishop²,

Astrin³

et al. 1989

J. Clin. Invest.

155

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Fabry disease, an X-linked recessive disorder of glycosphingolipid catabolism, results from the deficient activity of the lysosomal hydrolase, a-galactosidase. Southern hybridization analysis of the a-galactosidase gene in affected hemizygous males from 130 unrelated families with Fabry disease revealed six with different gene rearrangements and one with an exonic point mutation resulting in the obliteration of an Msp I restriction site. Five partial gene deletions were detected ranging in size from 0.4 to > 5.5 kb. Four of these deletions had breakpoints in intron 2, a region in the gene containing multiple Alu repeat sequences. A sixth genomic rearrangement was identified in which a region of about 8 kb, containing exons 2 through 6, was duplicated by a homologous, but unequal crossover event. The Msp I site obliteration, which mapped to exon 7, was detected in an affected hemizygote who had residual enzyme activity. Genomic amplification by the polymerase chain reaction and sequencing revealed that the obliteration resulted from a C to T transition at nucleotide 1066 in the coding sequence. This point mutation, the first identified in Fabry disease, resulted in an arginine356 to tryptophan3% substitution which altered the enzyme's kinetic and stability properties. The detection of these abnormalities provided for the precise identification of Fabry heterozygotes, thereby permitting molecular pedigree analysis in these families which revealed paternity exclusions and the first documented new mutations in this disease.

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“…Until now, at least nine females with FD have had successful pregnancy outcomes during ERT [14]. Gb3 deposits have been described in many renal cell types as early as 17 weeks of gestation [15] and have been described in the placental tissue of patients with FD [16]. There are still not enough studies to clarify whether the enzyme (product) passes the placental barrier [16].…”

Section: Discussionmentioning

confidence: 99%