Smn1, the survival motor neuron 1 gene, is crucial as its loss or deletion causes spinal muscular atrophy (SMA), a leading cause of early infant death [2,3,4,5,6,7,8,9]. The protein it produces, SMN, is ubiquitously expressed and essential for the development and survival of motor neurons [6].

Bi-allelic mutations of SMN1 lead to SMA [1]. Most SMA patients display homozygous absence of SMN1 exons 7 and 8 or exon 7 only among 5q13-linked SMA patients, with about 4% having a compound heterozygosity [3]. The number of SMN2 copies, a paralog of SMN1, modulates the SMA phenotype, but should not be used to predict SMA severity [3]. Genetic testing of SMN1 has enabled precise epidemiological studies, revealing that over 95% of affected patients are homozygous for SMN1 deletion [5]. New treatments, like nusinersen, onasemnogene abeparvovec, and risdiplam, target SMN2 to increase SMN protein levels [2,6,9].

In conclusion, Smn1 is essential for motor neuron development and survival, and its disruption leads to SMA. Understanding Smn1's role through genetic testing and research on its interaction with SMN2 has been crucial for developing treatments for this severe neuromuscular disease. [1,2,3,4,5,6,7,8,9]

References:

1. Chen, Xiao, Harting, John, Farrow, Emily, Pastinen, Tomi, Eberle, Michael A. 2023. Comprehensive SMN1 and SMN2 profiling for spinal muscular atrophy analysis using long-read PacBio HiFi sequencing. In American journal of human genetics, 110, 240-250. doi:10.1016/j.ajhg.2023.01.001. https://pubmed.ncbi.nlm.nih.gov/36669496/

2. Butchbach, Matthew E R. 2021. Genomic Variability in the Survival Motor Neuron Genes (SMN1 and SMN2): Implications for Spinal Muscular Atrophy Phenotype and Therapeutics Development. In International journal of molecular sciences, 22, . doi:10.3390/ijms22157896. https://pubmed.ncbi.nlm.nih.gov/34360669/

3. Wirth, B. . An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA). In Human mutation, 15, 228-37. doi:. https://pubmed.ncbi.nlm.nih.gov/10679938/

4. Kolb, Stephen J, Kissel, John T. . Spinal Muscular Atrophy. In Neurologic clinics, 33, 831-46. doi:10.1016/j.ncl.2015.07.004. https://pubmed.ncbi.nlm.nih.gov/26515624/

5. Nishio, Hisahide, Niba, Emma Tabe Eko, Saito, Toshio, Takeshima, Yasuhiro, Awano, Hiroyuki. 2023. Spinal Muscular Atrophy: The Past, Present, and Future of Diagnosis and Treatment. In International journal of molecular sciences, 24, . doi:10.3390/ijms241511939. https://pubmed.ncbi.nlm.nih.gov/37569314/

6. Reilly, Aoife, Chehade, Lucia, Kothary, Rashmi. 2022. Curing SMA: Are we there yet? In Gene therapy, 30, 8-17. doi:10.1038/s41434-022-00349-y. https://pubmed.ncbi.nlm.nih.gov/35614235/

7. Arnold, W David, Kassar, Darine, Kissel, John T. 2014. Spinal muscular atrophy: diagnosis and management in a new therapeutic era. In Muscle & nerve, 51, 157-67. doi:10.1002/mus.24497. https://pubmed.ncbi.nlm.nih.gov/25346245/

8. Lunn, Mitchell R, Wang, Ching H. . Spinal muscular atrophy. In Lancet (London, England), 371, 2120-33. doi:10.1016/S0140-6736(08)60921-6. https://pubmed.ncbi.nlm.nih.gov/18572081/

9. Gowda, Vasantha Lakshmi, Fernandez-Garcia, Miguel A, Jungbluth, Heinz, Wraige, Elizabeth. 2022. New treatments in spinal muscular atrophy. In Archives of disease in childhood, 108, 511-517. doi:10.1136/archdischild-2021-323605. https://pubmed.ncbi.nlm.nih.gov/36316089/