Eight novel mutations in the HEXA gene

Abstract

Purpose: To characterize novel mutations in the HEXA gene (α-subunit β-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. Conclusion: 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.