Khanbazi Ali, Beheshtian Maryam, Azad Maryam, Akbari Kelishomi Masoumeh, Afroozan Fariba, Fatehi Fatemeh, Noudehi Khadijeh, Zamanian Najafabadi Shima, Omrani Mohammadamin, Habibi Haleh, Taghdiri Maryam, Abdi Rad Isa, Nafissi Shahriar, Jankhah Aria, Yazdan Hilda, Daneshmand Parvaneh, Saberi Seyed Hosseinali, Kahrizi Kimia, Kariminejad Ariana, Najmabadi Hossein
Kariminejad - Najmabadi Pathology & Genetics Center, Tehran, Iran.
Genetics Research Center, University of Social Welfare & Rehabilitation Sciences, Tehran, Iran.
Sci Rep. 2024 Dec 2;14(1):29880. doi: 10.1038/s41598-024-76815-x.
Copy number variations in the SMN1 gene on chromosome 5 are the primary cause of Spinal Muscular Atrophy (SMA) disease, characterized by muscle weakness and degeneration due to impaired alpha motor neurons in the spinal cord. To obtain a comprehensive molecular understanding of the SMA, including carriers, silent carriers, and patients in the Iranian population, we analyzed data from 5224 individuals referred to Kariminejad - Najmabadi Pathology & Genetics Center, Tehran, Iran, between 2006 and 2023 using MLPA and quantitative RT-PCR methods. The carrier frequency of SMA was estimated to be 5.55%. Furthermore, 3.06% of SMA parents (n = 24) had two copies of the SMN1 gene. Among 725 patients, those with an earlier onset of SMA were more likely to have two copies of the SMN2 gene (46.45%) and no copies of the NAIP gene (49.36%). Among the 654 fetal samples screened for SMA, 22.33% were found to be affected, while 3.46% of their parents tested normal. These findings are valuable for genetic counseling, carrier screening, and prenatal diagnosis of SMA in Iran. Furthermore, they underscore the importance of CNV analysis of SMN1, SMN2, and NAIP genes for accurate diagnosis and prognosis of SMA.
5号染色体上SMN1基因的拷贝数变异是脊髓性肌萎缩症（SMA）的主要病因，其特征是由于脊髓中的α运动神经元受损而导致肌肉无力和退化。为了全面了解伊朗人群中SMA患者、携带者、沉默携带者的分子情况，我们使用多重连接探针扩增（MLPA）和定量逆转录聚合酶链反应（qRT-PCR）方法，分析了2006年至2023年间转诊至伊朗德黑兰卡里米内贾德 - 纳吉姆巴迪病理与遗传学中心的5224名个体的数据。SMA的携带者频率估计为5.55%。此外，3.06%的SMA患者父母（n = 24）有两个拷贝的SMN1基因。在725例患者中，SMA发病较早的患者更有可能有两个拷贝的SMN2基因（46.45%）且没有NAIP基因的拷贝（49.36%）。在654份筛查SMA的胎儿样本中，发现22.33%受到影响，而其父母中有3.46%检测结果正常。这些发现对于伊朗SMA的遗传咨询、携带者筛查和产前诊断具有重要价值。此外，它们强调了对SMN1、SMN2和NAIP基因进行拷贝数变异分析对于准确诊断和预测SMA的重要性。
