title: Tay-Sachs Carrier Screening by Enzyme and Molecular Analyses in the New York City Minority Population.
abstract: OBJECTIVE
  Carrier screening for Tay-Sachs disease is performed by sequence analysis of the HEXA gene and/or hexosaminidase A enzymatic activity testing. Enzymatic analysis (EA) has been suggested as the optimal carrier screening method, especially in non-Ashkenazi Jewish (non-AJ) individuals, but its utilization and efficacy have not been fully evaluated in the general population. This study assesses the reliability of EA in comparison with HEXA sequence analysis in non-AJ populations.
  
  
  METHODS
  Five hundred eight Hispanic and African American patients (516 samples) had EA of their leukocytes performed and 12 of these patients who tested positive by EA ("carriers") had subsequent HEXA gene sequencing performed.
  
  
  RESULTS
  Of the 508 patients, 25 (4.9%) were EA positive and 40 (7.9%) were inconclusive. Of the 12 patients who were sequenced, 11 did not carry a pathogenic variant and one carried a likely deleterious mutation (NM_000520.4(HEXA):c.1510C>T).
  
  
  CONCLUSIONS
  High inconclusive rates and poor correlation between positive/inconclusive enzyme results and identification of pathogenic mutations suggest that ethnic-specific recalibration of reference ranges for EA may be necessary. Alternatively, HEXA gene sequencing could be performed.
authors.affiliation: 1 Counsyl , South San Francisco, California.
authors.forename: Nikita
authors.initials: N
authors.lastname: Mehta
authors.affiliation: 1 Counsyl , South San Francisco, California.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Lazarin
authors.affiliation: 2 Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Columbia University Medical Center , New York, New York.
authors.forename: Erica
authors.initials: E
authors.lastname: Spiegel
authors.affiliation: 1 Counsyl , South San Francisco, California.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Berentsen
authors.affiliation: 2 Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Columbia University Medical Center , New York, New York.
authors.forename: Kelly
authors.initials: K
authors.lastname: Brennan
authors.affiliation: 1 Counsyl , South San Francisco, California.|2 Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Columbia University Medical Center , New York, New York.|3 Department of OBGYN-MFM, Columbia Doctors Midtown , New York, New York.
authors.forename: Jessica
authors.initials: J
authors.lastname: Giordano
authors.affiliation: 1 Counsyl , South San Francisco, California.
authors.forename: Imran S
authors.initials: IS
authors.lastname: Haque
authors.affiliation: 2 Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Columbia University Medical Center , New York, New York.
authors.forename: Ronald
authors.initials: R
authors.lastname: Wapner
mesh_terms: D001741:Black or African American / Q000235:genetics; D057075:Enzyme Assays / Q000379:methods*; D005006:Ethnicity / Q000235:genetics; D006580:Genetic Carrier Screening / Q000379:methods*; D005820:Genetic Testing / Q000379:methods; D006579:Heterozygote; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007585:Jews / Q000235:genetics; D009154:Mutation; D009519:New York City / Q000453:epidemiology; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D013661:Tay-Sachs Disease / Q000175:diagnosis / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D054820:beta-Hexosaminidase alpha Chain / Q000235:genetics* / Q000378:metabolism*
chemical_list: C518253:HEXA protein, human; D054820:beta-Hexosaminidase alpha Chain