Coulter-Mackie M B, Applegarth D A, Toone J, Vallance H
Department of Pediatrics, University of British Columbia, Vancouver, Canada.
Clin Biochem. 1997 Feb;30(1):57-61. doi: 10.1016/s0009-9120(96)00124-5.
To identify the molecular basis of arylsulfatase A deficiency in a family at risk for metachromatic leukodystrophy (MLD) and determine the genetic risk in the offspring.
Mutations in the arylsulfatase A gene were identified by PCR amplification and restriction enzyme digestion. Individuals had previously been tested for arylsulfatase A activity.
Assays of arylsulfatase A activity had resulted in ambiguous results for MLD carrier identification. DNA analysis clearly identified two MLD mutations in the family, and an unsuspected arylsulfatase A pseudodeficiency. The DNA information immediately clarified the MLD risk for the family and confirmed that a newborn with low arylsulfatase A activity was unaffected.
The overlap between activities for various combinations of MLD and pseudodeficiency alleles and the variability inherent in the assay of arylsulfatase A complicate the interpretation of activity levels in families at risk for MLD. Use of simple molecular biological tests for pseudodeficiency and the common MLD mutations in combination with the enzyme data can facilitate carrier identification and prenatal diagnosis.
确定一个有患异染性脑白质营养不良（MLD）风险的家族中芳基硫酸酯酶A缺乏的分子基础，并确定其后代的遗传风险。
通过聚合酶链反应（PCR）扩增和限制性内切酶消化来鉴定芳基硫酸酯酶A基因中的突变。此前已对个体进行芳基硫酸酯酶A活性检测。
芳基硫酸酯酶A活性检测对于MLD携带者鉴定的结果不明确。DNA分析明确鉴定出该家族中的两个MLD突变以及一个未被怀疑的芳基硫酸酯酶A假性缺乏。DNA信息立即明确了该家族的MLD风险，并证实一名芳基硫酸酯酶A活性低的新生儿未受影响。
MLD和假性缺乏等位基因的各种组合的活性之间的重叠以及芳基硫酸酯酶A检测中固有的变异性，使得对有MLD风险家族中活性水平的解释变得复杂。使用针对假性缺乏和常见MLD突变的简单分子生物学检测并结合酶数据，可以促进携带者鉴定和产前诊断。
