Prenatal diagnosis of Tay-Sachs disease for at-risk families

AB - The abnormalities in the gene coding for the β-hexosaminidase a subunit were analysed from fibroblast's RNAs of 42 Tay-Sachs patients (seven with adult or late onset of Tay-Sachs disease and 35 with infantile Tay-Sachs disease). After first strand synthesis by random priming, PCR was used to amplify in two overlapping fragments (868 and 949 bp) the entire coding region. These amplified products were first studied for changes in size by agarose gel electrophoresis to screen for splicing mutations leading to exon skipping or cryptic splice site activation. For each patient, the two overlapping cDNA fragments were subjected to chemical mismatch cleavage analysis using hydroxylamine to modify C-containing mismatches and osmium tetroxide to modify T-containing mismatches. DGGE was used to screen for mutations in the coding region spanning exon 2 to exon 6, a region putatively encompassing the active site and therefore a potential hot spot of mutations associated with Tay-Sachs disease. To increase the sensitivity of the technique, a 30 by GC-clamp has been added at the 5′ end of the sense oligonucleotide to amplify a fragment of 629 bp. The computerized analysis found that single base changes in domain spanning from nt 313 to nt 693 can be distinguished. Fragments displaying an altered melting behavior or a cleaved product were further analysed by direct sequencing of the amplified material. These methods as a whole allowed us to identify 30/38 alleles studied (79%) with 15 point mutations and one 4 by insertion detected. Thirteen alleles (34%) were known mutations with exon 1I insertion and Gly269 → Ser mutations accounting for four alleles each. Seventeen alleles (45%) carried 14 different novel mutations (two splicing and 12 missense mutations). The region scanned by DGGE contained seven out of the 30 identified alleles (23%) of which six carried novel mutations. The novel Tay-Sachs mutations detected in this study increase the number of mutant alleles identified in our laboratory to 22. These results provide further insight into the molecular heterogeneity of Tay-Sachs disease.

Here GNN posts abstracts to six articles on screening for Tay-Sachs disease. See
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You may have this test to check whether you are a Tay-Sachs carrier. If you are pregnant, both you and your partner can be tested. If both you and your partner are known carriers, DNA testing can diagnose Tay-Sachs disease in the fetus.


Tay-Sachs Disease Carrier Testing Protocol

Second-tier test for confirming a biochemical diagnosis ofTay-Sachs disease (TSD)
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Alternatively, full gene sequencing is available to evaluate formutations in all coding regions and exon/intron boundaries of the gene by orderingHEXAZ / Tay-Sachs Disease, Gene, Full Gene Analysis.


Tay-Sachs Disease Does this test have other names

Please Note: Tay-Sachs DNA testing should beperformed only as an adjunct to enzymatic testing. If an individualhas previously had enzymatic testing, please provide results. Ifsending blood for both DNA and enzyme testing, send two tubes.

Tay-Sachs Disease | Saint Luke's Health System

Tay-Sachs disease (TSD) is an autosomal-recessive, progressive, and ultimately fatal neurodegenerative disorder. Within the last 30 years, the discovery of the enzymatic basis of the disease, namely deficiency of the enzyme hexosaminidase A, made possible both enzymatic diagnosis of TSD and heterozygote identification. In the last decade, the cloning of the HEXA gene and the identification of more than 80 associated TSD-causing mutations has permitted molecular diagnosis in many instances. TSD was the first genetic condition for which community-based screening for carrier detection was implemented. As such, the TSD experience can be viewed as a prototypic effort for public education, carrier testing, and reproductive counseling for avoiding fatal childhood disease. More importantly, the outcome of TSD screening over the last 28 years offers convincing evidence that such an effort can dramatically reduce incidence of the disease.

Tay-Sachs Disease Mutation Analysis - Indiana …

This paper presents the findings of a community-based carrier screening program for Tay-Sachs disease, initiated on the University of Wisconsin-Madison campus in 1978. The Madison Community Tay-Sachs Screening Program (MCTSSP) is a collaborative, interdisciplinary program that organizes and conducts periodic screening for Tay-Sachs disease (TSD) for the purpose of identifying Tay-Sachs carriers. We present and analyze data on carrier detection with regard to various demographics, including family history of TSD, ancestry, gender, medication exposure, and illness. Individuals participating in the MCTSSP between 1978 and 1999 were primarily of the target population, and the carrier rate was within the expected range (1/25). Despite aggressive publicity efforts and a well-established program, attendance at the screens has declined. A recent survey of Jewish undergraduate students at the University of Wisconsin-Madison showed poor recall of family screen history and carrier status and reinforced the perception that utilization of the Madison screening program has been low. Ways to increase awareness of and interest in carrier screening for TSD are explored.