Shboul Mohammad, El-Khateeb Mohammed, Fathallah Rajaa, Al-Rashed Khadeeja
Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, Jordan.
National Center for Diabetes, Endocrinology and Genetics, Amman, Jordan.
J Matern Fetal Neonatal Med. 2025 Dec;38(1):2540463. doi: 10.1080/14767058.2025.2540463. Epub 2025 Aug 3.
Spinal muscular atrophy (SMA) is a life-threatening, neuromuscular disease caused by variants in the survival motor neuron 1 (SMN1) gene, which affects spinal motor neurons resulting in progressive muscle weakness and hypotonia. This study aimed to identify the genetic diagnosis of SMA, present the outcomes of prenatal diagnosis, and provide an estimate for a minimum prevalence of the disease in Jordan.
From 2007 through 2024, a total of 413 patients clinically suspected to have SMA and 243 at-risk prenatal cases were studied using diagnostic molecular testing. SMN1 exons 7 and 8 deletions were analyzed using either polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) (patients: = 308, fetuses: = 194) or multiplex ligation-dependent probe amplification (MLPA) (patients: = 105, fetuses: = 49). The copy number of SMN2 was determined for patients tested by MLPA.
Homozygous deletion of SMN1 exon 7 was identified in 59.3% (245/413) of patients. Among them, 73.5% ( = 180) had SMA type I, 22.9% ( = 56) type II, and 3.7% ( = 9) type III. MLPA confirmed the diagnosis in 60% (63/105) of patients, with SMN2 copy numbers correlating with disease severity. A minimum prevalence of SMA was predicted to be 2.09 per 100,000 population with an incidence of 0.73 per 10,000 live births. Results on prenatal diagnostic cases showed 70.8% (172/243) of fetuses were unaffected.
The study highlights the importance of SMA as a clinical health problem in Jordan and demonstrates MLPA as a reliable diagnostic tool. Our findings support the integration of SMA carrier screening into national newborn screening and premarital programs to enable early diagnosis, improve genetic counseling, and facilitate gene therapy options, ultimately improving overall patient outcomes and management.
脊髓性肌萎缩症（SMA）是一种由生存运动神经元1（SMN1）基因变异引起的危及生命的神经肌肉疾病，它影响脊髓运动神经元，导致进行性肌肉无力和肌张力减退。本研究旨在确定SMA的基因诊断，呈现产前诊断的结果，并估算约旦该疾病的最低患病率。
从2007年到2024年，共对413例临床疑似患有SMA的患者和243例高危产前病例进行了诊断性分子检测。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）（患者：n = 308，胎儿：n = 194）或多重连接依赖探针扩增（MLPA）（患者：n = 105，胎儿：n = 49）分析SMN1外显子7和8的缺失情况。对通过MLPA检测的患者测定SMN2的拷贝数。
在4 .13例患者中，59.3%（245/413）被鉴定为SMN1外显子7纯合缺失。其中，73.5%（n = 180）为I型SMA，22.9%（n = 56）为II型，3.7%（n = 9）为III型。MLPA在60%（63/105）的患者中确诊，SMN2拷贝数与疾病严重程度相关。预计SMA的最低患病率为每10万人中有2.09例，每10000例活产儿中的发病率为0.73例。产前诊断病例的结果显示，70.8%（172/243）的胎儿未受影响。
该研究强调了SMA作为约旦临床健康问题的重要性，并证明MLPA是一种可靠的诊断工具。我们的研究结果支持将SMA携带者筛查纳入国家新生儿筛查和婚前检查项目，以实现早期诊断、改善遗传咨询并促进基因治疗选择，最终改善患者的总体预后和管理。
