Frequency of the Tay-Sachs disease splice and insertion mutations in the UK Ashkenazi Jewish population
| Autor: | A H Fensom, M Bobrow, E C Landels, I H Ellis, Peter M. Green |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Heterozygote Population Molecular Sequence Data Biology medicine.disease_cause Polymerase Chain Reaction Exon Gene Frequency Genetics Lysosomal storage disease medicine Humans Hexosaminidase splice Genetic Testing education Genetics (clinical) Mutation education.field_of_study Splice site mutation Tay-Sachs Disease Base Sequence Tay-Sachs disease nutritional and metabolic diseases Exons medicine.disease Introns United Kingdom beta-N-Acetylhexosaminidases Jews North America Research Article |
| Zdroj: | Journal of medical genetics. 28(3) |
| ISSN: | 0022-2593 |
| Popis: | Tay-Sachs disease is a lethal neurodegenerative disorder caused by deficiency of the lysosomal enzyme beta-hexosaminidase A and inherited in an autosomal recessive fashion; carriers of the disease are 10 times more frequent in the Ashkenazi Jewish community than in the general population. Over 90% of North American Ashkenazi carriers tested have been shown to have either a splice site mutation at the boundary of exon 12 and intron 12 in the beta-hexosaminidase alpha subunit gene, or a 4 base pair insertion in exon 11. We describe simple assays involving amplification of DNA across these two mutation sites by polymerase chain reaction and the results of screening 75 subjects are given. The frequencies of the splice and insert mutations in 41 UK Ashkenazi carriers (20% to 80%, respectively) were similar to those found in the North American community. Twelve Ashkenazi subjects classified as non-carriers on enzyme assay were found to be negative for both mutations tested. All Ashkenazi carriers tested (both obligate carriers and those picked up by population screening) had either the splice or insert mutations; in contrast to this, only 21% of the non-Ashkenazi carriers had one or other of these mutations. It is concluded that within the carrier screening programmes for the Ashkenazi community, assays for the splice and insert mutations, together with an assay recently described for a mutation causing the rarer adult onset form of the disease, will prove useful as confirmatory tests for subjects who give positive or borderline results when screened on enzyme assay. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|