Improving accuracy of Tay Sachs carrier screening of the non-Jewish population: analysis of 34 carriers and six late-onset patients with HEXA enzyme and DNA sequence analysis.
The purpose of this study was to determine whether combining different testing modalities namely beta-hexosaminidase A (HEXA) enzyme analysis, HEXA DNA common mutation assay, and HEXA gene sequencing could improve the sensitivity for carrier detection in non-Ashkenazi (AJ) individuals. We performed a HEXA gene sequencing assay, a HEXA DNA common mutation assay, and a HEXA enzyme assay on 34 self-reported Tay-Sachs disease (TSD) carriers, six late-onset patients with TSD, and one pseudodeficiency allele carrier. Sensitivity of TSD carrier detection was 91% for gene sequencing compared with 91% for the enzyme assay and 52% for the DNA mutation assay. Gene sequencing combined with enzyme testing had the highest sensitivity (100%) for carrier detection. Gene sequencing detected four novel mutations, three of which are predicted to be disease causing [118.delT, 965A-->T (D322V), and 775A-->G (T259A)]. Gene sequencing is useful in identifying rare mutations in patients with TSD and their families, in evaluating spouses of known carriers for TSD who have indeterminate enzyme analysis and negative for common mutation analysis, and in resolving ambiguous enzyme testing results.
Park
Noh Jin
NJ
Molecular Genetics Department, Quest Diagnostics Nichols Institute, San Juan Capistrano, California 92690, USA.
Morgan
Craig
C
Sharma
Rajesh
R
Li
Yuanyin
Y
Lobo
Raynah M
RM
Redman
Joy B
JB
Salazar
Denise
D
Sun
Weimin
W
Neidich
Julie A
JA
Strom
Charles M
CM
D000328:Adult; D017668:Age of Onset; D004796:Clinical Enzyme Tests; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D013661:Tay-Sachs Disease / Q000175:diagnosis* / Q000201:enzymology / Q000208:ethnology / Q000235:genetics; D054820:beta-Hexosaminidase alpha Chain / Q000097:blood / Q000235:genetics*
C518253:HEXA protein, human; D054820:beta-Hexosaminidase alpha Chain