Eight novel mutations in the HEXA gene.
OBJECTIVE
To characterize novel mutations in the HEXA gene (alpha-subunit beta-hexosaminidase A).


METHODS
Subjects included participants in the California Tay-Sachs disease prevention program. DNA samples from 49 subjects (47 enzymatically defined carriers and 2 disease afflicted) who were negative for the four common disease-associated and the two pseudodeficient mutations, were subjected to single-strand conformation polymorphism (SSCP) analysis over 14 exons.


RESULTS
Targeted sequencing of the 39 electrophoretic variants from SSCP analysis revealed eight novel and deleterious mutations and 31 with previously described mutations. Six novel mutations were found in non-Jewish carriers, and two were found in two patients with infantile Tay-Sachs disease.


CONCLUSIONS
Identification of these eight novel mutations provides additional insight to the mutational spectrum for the HEXA gene. Furthermore, this knowledge should enhance diagnosis and prognosis for Tay-Sachs disease, carrier identification, and fundamental studies in structure/function relationships between this gene and its enzymatic product.
McGinniss
Matthew J
MJ
Department of Pediatrics, University of California San Diego, Genetic Services, Children's Hospital, San Diego, California, USA.
Brown
David H
DH
Fulwiler
Andrea
A
Marten
Molly
M
Lim-Steele
Joyce S T
JS
Kaback
Michael M
MM
D004252:DNA Mutational Analysis; D005091:Exons; D054818:Hexosaminidase A; D006801:Humans; D007585:Jews / Q000235:genetics; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D013661:Tay-Sachs Disease / Q000201:enzymology / Q000235:genetics; D001619:beta-N-Acetylhexosaminidases / Q000172:deficiency / Q000235:genetics*
D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases