A second mutation associated with apparent beta-hexosaminidase A pseudodeficiency: identification and frequency estimation.
A second mutation associated with apparent beta-hexosaminidase A pseudodeficiency: identification and frequency estimation.
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与明显的β-己糖胺酶A假性缺陷相关的第二个突变：识别和频率估计。
DOI：
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发表时间：
1993
影响因子：
9.8
通讯作者：
B. Triggs
中科院分区：
文献类型：
--
作者：
Z. Cao;Marvin R. Natowicz;Michael M. Kaback;J. Lim;E. Prence;David H. Brown;T. Chabot;B. Triggs
由HEXA基因突变引起的β-氨基己糖苷酶A（Hex A）活性不足通常会导致泰-萨克斯病。然而，缺乏针对合成底物的Hex A活性的健康个体（即，伪缺陷的个体）已经被描述。最近，一个明显的良性C739-T（Arg 247 Trp）突变被发现与Hex A水平的个人之间的Tay-Sachs病的携带者难以区分。当该等位基因与第二个“致病”等位基因处于复合杂合性时，会导致Hex A假性缺陷。我们检查了一个健康的42岁的HEXA基因谁是Hex A缺陷，但没有C739到T突变。PCR扩增HEXA外显子，并通过使用限制性酶切或单链凝胶电泳分析产物的突变。在一条染色体上发现了与成人发病的GM 2神经节苷脂沉积症相关的G805-to-A（Gly 269 Ser）突变。在第二条染色体上发现了一个新的突变，C745-to-T（Arg 249 Trp）。在另外4/63（6%）非犹太人和0/218德系犹太人酶定义的载体中检测到这种突变。虽然Arg 249 Trp的改变可能导致晚发型GM 2神经节苷脂沉积症，但任何表型都必须非常轻微。这种新的突变和良性C739-T突变一起占非犹太酶定义的携带者的约38%。由于使用经典的生化筛查方法无法区分C739-to-T和C745-to-T突变的携带者与致病等位基因的携带者，因此应针对非犹太酶定义的杂合子提供基于DNA的这些突变分析，然后再提供明确的咨询。
Deficient activity of beta-hexosaminidase A (Hex A), resulting from mutations in the HEXA gene, typically causes Tay-Sachs disease. However, healthy individuals lacking Hex A activity against synthetic substrates (i.e., individuals who are pseudodeficient) have been described. Recently, an apparently benign C739-to-T (Arg247Trp) mutation was found among individuals with Hex A levels indistinguishable from those of carriers of Tay-Sachs disease. This allele, when in compound heterozygosity with a second "disease-causing" allele, results in Hex A pseudodeficiency. We examined the HEXA gene of a healthy 42-year-old who was Hex A deficient but did not have the C739-to-T mutation. The HEXA exons were PCR amplified, and the products were analyzed for mutations by using restriction-enzyme digestion or single-strand gel electrophoresis. A G805-to-A (Gly269Ser) mutation associated with adult-onset GM2 gangliosidosis was found on one chromosome. A new mutation, C745-to-T (Arg249Trp), was identified on the second chromosome. This mutation was detected in an additional 4/63 (6%) non-Jewish and 0/218 Ashkenazi Jewish enzyme-defined carriers. Although the Arg249Trp change may result in a late-onset form of GM2 gangliosidosis, any phenotype must be very mild. This new mutation and the benign C739-to-T mutation together account for approximately 38% of non-Jewish enzyme-defined carriers. Because carriers of the C739-to-T and C745-to-T mutations cannot be differentiated from carriers of disease-causing alleles by using the classical biochemical screening approaches, DNA-based analyses for these mutations should be offered for non-Jewish enzyme-defined heterozygotes, before definitive counseling is provided.
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德系犹太人和非犹太成年 GM2 神经节苷脂病患者具有共同的遗传缺陷。
影响因子：
9.8
作者：
Navon,R;Kolodny,EH;Mitsumoto,H;Thomas,GH;Proia,RL
通讯作者：
Proia,RL
德系犹太裔患者成人发病和慢性 GM2 神经节苷脂增多症的分子基础：β-己糖胺酶 α 亚基的 269 位丝氨酸取代甘氨酸。
DOI：
10.1073/pnas.86.7.2413
发表时间：
1989
影响因子：
11.1
作者：
Paw,BH;Kaback,MM;Neufeld,EF
通讯作者：
Neufeld,EF
非犹太泰萨克斯携带者中常见的假缺陷等位基因：对携带者筛查的影响。
影响因子：
9.8
作者：
Triggs-Raine,BL;Mules,EH;Kaback,MM;Lim-Steele,JS;Dowling,CE;Akerman,BR;Natowicz,MR;Grebner,EE;Navon,R;Welch,JP
通讯作者：
Welch,JP
Tay-Sachs 筛查计划中确定的犹太和非犹太携带者中三个 Hex A 突变等位基因的频率。
影响因子：
9.8
作者：
Paw,BH;Tieu,PT;Kaback,MM;Lim,J;Neufeld,EF
通讯作者：
Neufeld,EF
临床正常个体中己糖胺酶 A 的两种异常。
影响因子：
9.8
作者：
Grebner,EE;Mansfield,DA;Raghavan,SS;Kolodny,EH;d'Azzo,A;Neufeld,EF;Jackson,LG
通讯作者：
Jackson,LG