Modification of phenotype by SMN2 copy numbers in two Chinese families with SMN1 deletion in two continuous generations.
Modification of phenotype by SMN2 copy numbers in two Chinese families with SMN1 deletion in two continuous generations.
复制标题
DOI：
10.1016/j.cca.2012.07.020
复制
发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Wan-Jin Chen;Jin He;Qi-Jie Zhang;Qi-fang Lin;Ya-Fang Chen;Xiao-Zhen Lin;Min-ting Lin;S. Murong;Ning Wang
中科院分区：
文献类型：
--
作者：
Wan-Jin Chen;Jin He;Qi-Jie Zhang;Qi-fang Lin;Ya-Fang Chen;Xiao-Zhen Lin;Min-ting Lin;S. Murong;Ning Wang
背景儿童脊髓性肌萎缩症(SMA)是一种致死性常染色体隐性遗传性疾病，由运动神经元存活基因1(SMN1)突变引起。大多数患者早期死亡或严重残疾，这部分解释了SMA连续两代的稀缺性。越来越多的证据表明，SMN1拷贝数是SMA的一个修饰符，但在大多数散发性患者中，表型判断的偏差可能会大大降低基因-表型分析的准确性。方法我们在连续两代中发现两个SMN1缺失个体，家庭1的父女和家庭2的母女被确定为SMN1基因缺失的纯合子。结果定量分析表明，家系1的父亲有3个拷贝的SMN1，其女儿只有2个拷贝，家系2的母亲有3个拷贝的SMN1，而患病的女儿只有2个拷贝的SMN 2；我们还对家系1进行了产前预测，并在我们的建议下出生了一个健康的男孩。结论由于同一家庭中不同世代的患者的表型明显不同，基因-表型分析的结果可能更令人信服，这有力地支持了SMN2是SMA的重要修饰物的假说，在产前诊断时应考虑SMN2的拷贝数。
BACKGROUNDAs a lethal autosomal recessive hereditary disorder, childhood spinal muscular atrophy (SMA) is caused by mutations of the survival motor neuron 1 (SMN1) gene. Most of the patients died at early stage or were seriously disabled, which accounts partly for the scarcity of two continuous generations with SMA. Increasing evidence indicated that SMN2 copy number was a modifier of SMA, but in majority of sporadic patients, the bias of phenotype judgments may largely reduce the accuracy of genotype–phenotype analysis.METHODSWe presented two families with SMN1-deleted individuals in two continuous generations, the father and daughter of family 1 and the mother and daughter of family 2 were determined to be homozygous for the deletion of the SMN1 gene. Quantitative analysis of SMN1 and SMN2 was carried out by real-time fluorescence quantitative PCR and multiplex ligation-dependent probe amplification.RESULTSQuantitative analysis showed that the father of family 1 possessed three copies of SMN2, and his daughter had only two SMN2 copies; the slightly affected mother of family 2 had three copies of SMN2, but her sick daughter had only two copies of SMN2; we also performed prenatal prediction for family 1 and a healthy boy was born under our suggestion.CONCLUSIONFor the phenotypes of patients from different generations within the same family are obviously different, the results of a genotype–phenotype analysis may be more convincing, which strongly support the hypothesis that SMN2 is an important modifier for SMA, and SMN2 copy number should be considered in the prenatal diagnosis situation.