PDF(Pubmed)
Abstract：
During the expanded neonatal screening program conducted in 2023, we analyzed samples obtained from 1,227,130 out of 1,256,187 newborns in the Russian Federation in order to detect 5q spinal muscular atrophy (5q SMA). Within the 253-sample risk group formed based on the results of the first screening stage, 5 samples showed a discrepancy between the examination results obtained via various screening methods and quantitative MLPA (used as reference). The discrepancy between the results was caused by the presence of either a c.835-18C>T intronic variant or a c.842G>C p.(Arg281Thr) missense variant in the SMN1 gene, both of which are located in the region complementary to the sequences of annealing probes for ligation and real-time PCR. Three newborns had the c.835-18C>T variant in a compound heterozygous state with a deletion of exons 7-8 of the SMN1 gene, one newborn with two copies of the SMN1 gene had the same variant in a heterozygous state, and one newborn had both variants-c.835-18C>T and c.842G>C p.(Arg281Thr)-in a compound heterozygous state. Additional examination was carried out for these variants, involving segregation analysis in families, carriage analysis in population cohorts, and RNA analysis. Based on the obtained results, according to the ACMG criteria, the c.835-18C>T intronic variant should be classified as likely benign, and the c.842G>C p.(Arg281Thr) missense substitution as a variant of uncertain clinical significance. All five probands are under dynamic monitoring. No 5q SMA symptoms were detected in these newborns neonatally or during a 1-year follow-up period.
摘要：
在2023年进行的扩大新生儿筛查计划中，我们分析了从俄罗斯联邦1,256,187名新生儿中的1,227,130名获得的样本，以检测5q脊髓性肌萎缩症（5qSMA）。在根据第一阶段筛选结果形成的253个样本的风险组中，5个样品显示通过各种筛选方法获得的检查结果与定量MLPA(用作参考)之间的差异。结果之间的差异是由于SMN1基因中存在c.835-18C>T内含子变体或c.842G>Cp。（Arg281Thr）错义变体，两者都位于与用于连接和实时PCR的退火探针的序列互补的区域中。三个新生儿具有复合杂合状态的c.835-18C>T变体，SMN1基因外显子7-8缺失，一个具有两个SMN1基因拷贝的新生儿在杂合状态下具有相同的变异，一名新生儿具有两种变体-c.835-18C>T和c.842G>Cp。（Arg281Thr）-处于复合杂合状态。对这些变体进行了额外的检查，涉及家庭中的种族隔离分析，人口队列中的运输分析，和RNA分析。根据获得的结果，根据ACMG标准,c.835-18C>T内含子变体应归类为良性，和c.842G>Cp。（Arg281Thr）错义替换为不确定临床意义的变体。所有五个先证者都受到动态监测。在这些新生儿中或在1年随访期间未检测到5qSMA症状。
