Population screening and cascade testing for carriers of SMA
Population screening and cascade testing for carriers of SMA
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DOI：
10.1038/sj.ejhg.5201821
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发表时间：
2007-07-01
影响因子：
5.2
通讯作者：
du Sart, Desiree
中科院分区：
文献类型：
--
作者：
Smith, Melanie;Calabro, Vanessa;du Sart, Desiree
脊髓性肌萎缩症（SMA）是最常见的常染色体隐性遗传疾病之一，由运动神经元生存基因1（SMN 1）的两个拷贝缺失引起。SMA携带者的识别对于有家族史的个人和一般人群具有重要意义。SMA携带者是完全健康的，大多数人直到他们有一个受影响的孩子才知道他们的携带者状态。共有422人被研究以确定SMA携带者。该队列包括117名SMN 1同源缺失儿童的父母（94%是携带者，6%有两个SMN 1拷贝;在这些个体中，七分之二的人具有“2+0”基因型，七分之二的人正常但有携带从头缺失的儿童，七分之三的人未解决），158名个体具有显著的SMA家族史。（47%有一个SMN 1拷贝，49%有两个SMN 1拷贝，4%有三个SMN 1拷贝）和146名没有SMA家族史的个体（90%有两个SMN 1拷贝，2%有一个SMN 1拷贝，8%有三个SMN 1拷贝）。澳大利亚人群中的SMA携带者频率似乎为1/49，双拷贝SMN 1等位基因和从头缺失突变的频率均至少为1.7%。一种涉及定量分析、连锁分析和遗传风险评估（GRA）的多模式方法有助于解决有家族史的个体以及普通人群中SMA携带者的状况，为夫妇提供更好的计划生育选择。
Spinal muscular atrophy (SMA) is one of the most common autosomal-recessive diseases, caused by absence of both copies of the survival motor neuron 1 (SMN1) gene. Identification of SMA carriers has important implications for individuals with a family history and the general population. SMA carriers are completely healthy and most are unaware of their carrier status until they have an affected child. A total of 422 individuals have been studied to identify SMA carriers. This cohort included 117 parents of children homozygously deleted for SMN1 (94% were carriers and 6% had two copies of SMN1; of these individuals, two in seven had the '2+0' genotype, two in seven were normal but had children carrying a de novo deletion and three in seven were unresolved), 158 individuals with a significant family history of SMA (47% had one copy, 49% had two copies and 4% had three copies of SMN1) and 146 individuals with no family history of SMA (90% had two copies, 2% had one copy and 8% had three copies of SMN1). The SMA carrier frequency in the Australian population appears to be 1/49 and the frequency of two-copy SMN1 alleles and de novo deletion mutations are both at least 1.7%. A multimodal approach involving quantitative analysis, linkage analysis and genetic risk assessment (GRA), facilitates the resolution of SMA carrier status in individuals with a family history as well as individuals of the general population, providing couples with better choices in their family planning.