Document Detail

A mutation common in non-Jewish Tay-Sachs disease: frequency and RNA studies.
MedLine Citation:
PMID:  1301938     Owner:  NLM     Status:  MEDLINE    
Tay-Sachs disease (TSD) is an autosomal recessive genetic disorder resulting from mutation of the HEXA gene encoding the alpha-subunit of the lysosomal enzyme, beta-N-acetylhexosaminidase A (Hex A). We have discovered that a Tay-Sachs mutation, IVS-9 + 1 G-->A, first detected by Akli et al. (Genomics 11:124-134, 1991), is a common disease allele in non-Jewish Caucasians (10/58 alleles examined). A PCR-based diagnostic test, which detects an NlaIII site generated by the mutation, revealed a frequency among enzyme-defined carriers of 9/64 (14%). Most of those carrying the allele trace their origins to the United Kingdom, Ireland, or Western Europe. It was not identified among 12 Black American TSD alleles or in any of 18 Ashkenazi Jewish, enzyme-defined carriers who did not carry any of the mutations common to this population. No normally spliced RNA was detected in PCR products generated from reverse transcription of RNA carrying the IVS-9 mutation. Instead, the low levels of mRNA from this allele were comprised of aberrant species resulting from the use of either of two cryptic donor sites, one truncating exon 9 and the other within IVS-9, spliced to exon 10. Numerous additional splice products were detected, most involving skipping of one or more surrounding exons. Together with a recently identified allele responsible for Hex A pseudodeficiency (Triggs-Raine et al. Am J Hum Genet, 1992), these two alleles accounted for almost 50% (29/64) of TSD or carrier alleles ascertained by enzyme screening tests in non-Jewish Caucasians.
B R Akerman; J Zielenski; B L Triggs-Raine; E M Prence; M R Natowicz; J S Lim-Steele; M M Kaback; E H Mules; G H Thomas; J T Clarke
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Human mutation     Volume:  1     ISSN:  1059-7794     ISO Abbreviation:  Hum. Mutat.     Publication Date:  1992  
Date Detail:
Created Date:  1993-06-10     Completed Date:  1993-06-10     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9215429     Medline TA:  Hum Mutat     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  303-9     Citation Subset:  IM    
McGill University-Montreal Children's Hospital Research Institute, Quebec, Canada.
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MeSH Terms
Base Sequence
DNA / genetics
DNA Mutational Analysis
Hexosaminidase A
Molecular Sequence Data
Point Mutation
Polymerase Chain Reaction
RNA, Messenger / genetics
Tay-Sachs Disease / diagnosis,  enzymology,  genetics*
beta-N-Acetylhexosaminidases / deficiency,  genetics
Grant Support
Reg. No./Substance:
0/RNA, Messenger; 9007-49-2/DNA; EC A; EC

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