Mehta Nikita, Lazarin Gabriel A, Spiegel Erica, Berentsen Kathleen, Brennan Kelly, Giordano Jessica, Haque Imran S, Wapner Ronald
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.
Genet Test Mol Biomarkers. 2016 Sep;20(9):504-9. doi: 10.1089/gtmb.2015.0302. Epub 2016 Jun 30.
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.
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.
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).
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.
通过对HEXA基因进行序列分析和/或进行己糖胺酶A酶活性检测来开展泰-萨克斯病的携带者筛查。酶学分析（EA）被认为是最佳的携带者筛查方法，尤其是在非阿什肯纳兹犹太人群体（非AJ）中，但在普通人群中其应用和效果尚未得到充分评估。本研究评估了在非AJ人群中EA与HEXA序列分析相比的可靠性。
对508名西班牙裔和非裔美国患者（516份样本）的白细胞进行了EA检测，其中12名EA检测呈阳性的患者（“携带者”）随后进行了HEXA基因测序。
在508名患者中，25名（4.9%）EA检测呈阳性，40名（7.9%）结果不确定。在进行测序的12名患者中，11名未携带致病变异，1名携带可能有害的突变（NM_000520.4(HEXA):c.1510C>T）。
高不确定率以及阳性/不确定酶学结果与致病变异鉴定之间的低相关性表明，可能有必要对EA的参考范围进行特定种族的重新校准。或者，可以进行HEXA基因测序。
