SPECIFICITY AND SENSITIVITY OF HEXOSAMINIDASE ASSAYS AND DNA ANALYSIS FOR THE DETECTION OF TAY-SACHS DISEASE GENE CARRIERS AMONG ASHKENAZIC JEWS

被引:22
作者
FERNANDES, MJG
KAPLAN, F
CLOW, CL
HECHTMAN, P
SCRIVER, CR
机构
[1] MCGILL UNIV,MONTREAL CHILDRENS HOSP,RES INST,DEBELLE LAB BIOCHEM GENET,2300 TUPPER ST,RM A-709,MONTREAL H3H 1P3,QUEBEC,CANADA
[2] MCGILL UNIV,DEPT BIOL,CTR HUMAN GENET,MONTREAL H3H 1P3,QUEBEC,CANADA
[3] MCGILL UNIV,DEPT PEDIAT,CTR HUMAN GENET,MONTREAL H3H 1P3,QUEBEC,CANADA
关键词
GENETIC SCREENING; HEXA MUTATIONS; POPULATION GENETICS;
D O I
10.1002/gepi.1370090303
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Tay-Sachs disease (TSD), a neurodegenerative disorder resulting from a deficiency of the lysosomal enzyme hexosaminidase A (HexA), clusters in Ashkenazic Jews. Population-based screening programs to detect carriers of TSD genes by means of HexA assays have been active since the 1970s. The recent characterization of 3 mutations in the HEXA gene (in exon 7, exon 11, and intron 12), which account for over 90% of HEXA mutations in Ashkenazim, appeared to offer better options for screening and diagnosis. The relative frequencies of the three mutations in Montreal are similar to those reported in four other North American populations. We compared enzyme and DNA analyses to determine specificity and sensitivity of each test when the other was used as the confirmatory procedure. Neither procedure has a sensitivity of 1.0. Maximum sensitivity and specificity were achieved by using both tests together. The findings here are likely to apply to most cases where the variant screened enzyme phenotype can result from more than one mutation.
引用
收藏
页码:169 / 175
页数:7
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