Homozygous SMN1 deletions in unaffected family members and modification of the phenotype by SMN2
Homozygous SMN1 deletions in unaffected family members and modification of the phenotype by SMN2
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DOI：
10.1002/ajmg.a.30251
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发表时间：
2004-10-15
影响因子：
2
通讯作者：
Hejmanowski, AQ
中科院分区：
文献类型：
--
作者：
Prior, TW;Swoboda, KJ;Hejmanowski, AQ
脊髓性肌萎缩症是一种常见的常染色体。由SMN1基因纯合缺失引起的隐性神经肌肉疾病。SMN1基因的缺失已被证明在所有类型的SMA中都存在，无论是儿童还是成人。在极少数情况下，也发现无症状的家庭成员存在SMN1基因的纯合子突变，这表明表型修饰基因的作用。我们描述了三个不相关的无症状个体，他们有SMA家族史，他们被证明有SMN1纯合子缺失。定量研究表明，这三个个体都增加了SMN2拷贝数。这些案例不仅支持SMN2在改变表型方面的作用，而且我们的数据还表明，与SMN1基因5个拷贝一致的表达水平可能足以弥补SMN1基因的缺失。最后，在类似描述的病例中，SMN2基因拷贝数的测量可能提供有价值的预后信息。(C)2004年Wiley-Liss公司
Spinal muscular atrophy is a common autosomal. recessive neuromuscular disorder caused by the homozygous loss of the SMN1 gene. The absence of the SMN1 gene has been shown to occur in all types of SMA, childhood and adult forms. In rare cases, asymptomatic family members have also been found with homozygous mutations in the SMN1 gene, suggesting a role for phenotypic modifiers. We describe three unrelated asymptomatic individuals, with family histories of SMA, who were shown to have the homozygous SMN1 deletion. Quantitative studies indicated that the three individuals all had increased SMN2 copy numbers. These cases not only support the role of SMN2 in modifying the phenotype, but our data also demonstrate that expression levels consistent with five copies of the SMN2 genes maybe enough to compensate for the absence of the SMN1 gene. Lastly, in cases similar to the ones described, the measurement of the SMN2 gene copy number may provide valuable prognostic information. (C) 2004 Wiley-Liss, Inc.