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- Title
Ten novel mutations in the HEXA gene in non-Jewish Tay — Sachs patients.
- Authors
Akli, Said; Chomel, Jean-Claude; Lacorte, Jean-Marc; Bachner, Lucien; Axel; Poenaru, Livia
- Abstract
The heterogeneity of mutations causing Tay—Sachs disease in non-Jewish populations requires efficient techniques allowing the simultaneous screening for both known and novel mutations. β-hexosaminidase mRNA isolated from cultured fibroblasts of 19 Tay-Sachs patients (7 with adult or late onset form of the disease and 12 with infantile Tay-Sachs disease) was amplified by cDNA—PCR in two overlapping segments spanning the entire coding sequence. We used chemical mismatch cleavage (CMC), denaturing gradient gel electrophoresis (DGGE) and direct sequencing of amplified fragments displaying a cleaved product or an altered melting behavior to screen the HEX A gene for mutations and to determine their distribution and frequency in the non-Jewish Tay—Sachs patients. These methods allowed us to identify 31 out of 38 alleles studied (82%). In addition to 9 previously described mutations (the 4 bp insertion in exon 11, G to A transitions at codons 170, 269, 482, 499 and 504, C to T transition at codon 499 and 504 and a GT to AT transition at the donor site of intron 9), we have identified 10 novel mutations. These include 1 donor splice site defect in intron 6, 8 missense mutations at non-randomly distributed conserved residues and a 2 bp deletion in exon 4. These results confirm the extreme molecular heterogeneity of mutations causing Tay—Sachs disease in non-Jewish population. The strategy used should be profitable for identifying mutations in large genes and for diagnostic purposes.
- Publication
Human Molecular Genetics, 1993, Vol 2, Issue 1, p61
- ISSN
0964-6906
- Publication type
Article