Prenatal diagnosis for Tay‐Sachs disease using chorionic villus sampling

Abstract

Prenatal diagnosis for Tay-Sachs disease was performed on 25 patients using chorionic villus sampling (CVS). Nineteen were diagnosed as normal, and six were affected. Normal villus extracts had both hexosaminidase (hex) A and B activity, as determined by Cellogel and polyacrylamide gel electrophoresis, while extracts from affected fetuses had only hex B activity. Compared to cultured amniotic fluid cells or fibroblasts, villi contained less hex A. Hex A levels in fresh villi and cultured trophoblasts were roughly comparable.

First trimester chorionic villi sampling and direct chromosome preparations

“…The biochemical disorders that are currently diagnosable by CVS include a and B thalassemia, Tay-Sachs disease, GMI gangliosidosis type 1, Mucopolysaccharidosis type VI, Hunters syndrome, and Krabbe's disease (Williamson et al 1981, Old et al 1982, Grebner & Jackson 1985, Goossens et al 1983, Poenaru et al 1984, Kleijer et al 1984a, b, Gatti et al 1985. At present alpha fetoprotein values cannot be determined from villi samples and normal values for maternal serum AFP levels for 9-11 weeks gestation are currently not available.…”

Use of 4‐methylumbelliferyl‐6‐sulpho‐2‐acetamido‐2‐deoxy‐β‐D‐glucopyranoside for prenatal diagnosis of tay‐sachs disease using chorionic villi

“…Chorionic villi were obtained by transcervical aspiration and extracts were prepared by freezing and thawing in 0.9 per cent NaCl as described (Grebner and Jackson, 1985). 4MUGlcNAc-6-S04 was synthesized as described (Inui and Wenger, 1984) or obtained from the HSC Research Development Corporation, Toronto, Canada.…”

“…For the qualitative test, the bottom of a small petri dish (60 x 15 nun) was covered with filter paper moistened with citrate-phosphate buffer on which was placed an 18 x 25 mm rectangle of Cellogel 500 (Chemetron, Milan) equilibrated in a solution of 4MUGlcNAc-6-S04 (2.5 mM in citrate-phosphate buffer). A small piece of villous tissue from the patient was freed of maternaI decidua as described (Grebner and Jackson, 1985), rinsed first in citrate-phosphate buffer, then in a solution of 4MUGlcNAc-6-S04, and placed on the 4MUG1cNAc-6-SO4-impregnated Cellogel strip. A piece of normal and affected villi was treated similarly and placed on the same strip as controls.…”

“…Assays for hex A using 4MUGlcNAc-6-S04 (or its nitrophenyl analogue) have been applied in a variety of situations for heterozygote detection or diagnosis of Tay-Sachs disease (Bayleran et al, 1984;Fuchs et al, 1983;Inui and Wenger, 1984;Li et al, 1983;Ben-Yoseph et al, 1985). We report here that 4MUGlcNAc-6-SO, can also be used to detect hex A in chorionic villi, thus extending the usefulness of this newly emerging approach to prenatal diagnosis (Grebner and Jackson, 1985). Two methods are described.…”

Obituary: Laird Jackson

“…Jefferson had one of the first centers in the country performing amniocentesis for prenatal diagnosis: both for karyotype and—as the field developed—biochemical diagnosis. As Tay Sachs carrier screening became available, Laird worked with Gene Grebner not only to develop the laboratory expertise to screen but also to engage with the Jewish community to implement community‐based screening and prenatal diagnosis …”