Faculty of Nutrition, Kobe Gakuin University, 518 Arise, Ikawadani-cho, Nishi-ku, Kobe 651-2180, Japan.
Division of Physiology, Shinko Hospital, 1-4-47 Wakinohama-cho, Chuo-ku, Kobe 651-0072, Japan.
Genes (Basel). 2023 Nov 29;14(12):2159. doi: 10.3390/genes14122159.
The survival motor neuron 2 () gene is a recognized modifier gene of spinal muscular atrophy (SMA). However, our knowledge about the role of -other than its modification of SMA phenotypes-is very limited. Discussions regarding the relationship between homozygous deletion and motor neuron diseases, including amyotrophic lateral sclerosis, have been mainly based on retrospective epidemiological studies of the diseases, and the precise relationship remains inconclusive. In the present study, we first estimated that the frequency of homozygous deletion was ~1 in 20 in Japan. We then established a real-time polymerase chain reaction (PCR)-based screening method using residual dried blood spots to identify infants with homozygous deletion. This method can be applied to a future prospective cohort study to clarify the relationship between homozygous deletion and motor neuron diseases. In our real-time PCR experiment, both PCR (low annealing temperatures) and blood (high hematocrit values and low white blood cell counts) conditions were associated with incorrect results (i.e., false negatives and positives). Together, our findings not only help to elucidate the role of , but also aid in our understanding of the pitfalls of current SMA newborn screening programs for detecting homozygous deletions.
运动神经元存活 2 号（）基因是公认的脊髓性肌萎缩症（SMA）修饰基因。然而，我们对其除了修饰 SMA 表型之外的作用知之甚少。关于纯合缺失与包括肌萎缩侧索硬化症在内的运动神经元疾病之间关系的讨论主要基于对这些疾病的回顾性流行病学研究，其确切关系仍不确定。在本研究中，我们首先估计纯合缺失的频率在日本约为 1/20。然后，我们建立了一种基于实时聚合酶链反应（PCR）的筛查方法，使用残留的干血斑来识别纯合缺失的婴儿。该方法可应用于未来的前瞻性队列研究，以阐明纯合缺失与运动神经元疾病之间的关系。在我们的实时 PCR 实验中，PCR（低退火温度）和血液（高红细胞压积值和低白细胞计数）条件均与错误结果（即假阴性和阳性）相关。总之，我们的研究结果不仅有助于阐明的作用，还帮助我们了解当前用于检测纯合缺失的 SMA 新生儿筛查程序的缺陷。
