Gaucher disease: Gene frequencies and genotype/phenotype correlations
Gaucher disease: Gene frequencies and genotype/phenotype correlations
复制标题
DOI：
10.1089/gte.1997.1.5
复制
发表时间：
1997-06-01
期刊：
影响因子：
--
通讯作者：
Grabowski, GA
中科院分区：
文献类型：
--
作者：
Grabowski, GA
戈谢病是最常见的溶酶体贮积病，在德系犹太人中发病率最高。在受影响的患者中已鉴定出超过 100 个突变等位基因，但四种等位基因（称为 N370S、L444P、84GG 和 IVS2）在该人群中具有显着的频率。在受影响的患者中，基因型数据显示单个 N370S 等位基因的存在可诊断 1 型或非神经病性变异，而 L444P/L444P 基因型与 1 型或非神经病性变异高度相关。针对白种人人群，大规模筛查研究还表明，受影响的德系犹太人患者群体中 N370S/N370S 基因型的患病率被显着低估（接近两倍）。这些结果表明，N370S/N370S基因型为戈谢病表型的发展提供了必要但不充分的条件，基因型/表型相关性和基因频率对高危夫妇的遗传咨询和受影响患者的未来治疗需求具有显着影响。
Gaucher disease is the most prevalent lysosomal storage disease and has its highest incidence in the Ashkenazi Jewish population. Over 100 mutant alleles have been identified in affected patients, but four alleles, termed N370S, L444P, 84GG, and IVS2, have significant frequencies in this population, In affected patients, genotype data show that the presence of a single N370S allele is diagnostic of the type 1 or nonneuronopathic variant, whereas the L444P/L444P genotype is highly associated with neuronopathic variants in the Caucasian population, Large screening studies also indicate a significant underestimation (similar to two-fold) of the prevalence of the N370S/N370S genotype in the affected Ashkenazi Jewish patient population. These results indicate that the N370S/N370S genotype provides a necessary but not sufficient condition for the development of the Gaucher disease phenotype, The genotype/phenotype correlations and gene frequencies have significant impact on genetic counseling of at-risk couples and the future need for therapy of affected patients.