Rare disease spinal muscular atrophy pathogenic gene SMN1 molecular diagnostic standard

Spinal muscular atrophy (SMA) is an autosomal recessive degenerative neuromuscular disease caused by the degeneration of motor neurons in the anterior horn of the spinal cord. The main clinical feature is muscle weakness and muscle atrophy caused by degeneration and loss of motor neurons in the anterior horn of the spinal cord, which can be fatal and disabled. The incidence of SMA in Chinese newborns is 1/9788, and the population carrier rate is as high as 1/50.

Introduction to SMA

SMA is a monogenic disease, that is, a disease caused by abnormalities in a single gene. It is known that the genetic pathogenic mode of SMA is autosomal recessive (AR).

The causative gene of SMA is the motor neuron survival gene (Survival motor neuron, SMN) located on 5q13. The structure of this region is complex, and there are repeated sequences and numerous pseudogene clusters, which can easily cause gene deletion and conversion. The telomeric and centromeric copies of the gene are nearly identical and encode the same protein; however, mutations in the gene, the telomeric copy, are associated with spinal muscular atrophy, and mutations in the centromeric copy do not cause the disease. Centromeric copies can be modifiers of diseases caused by mutations in telomeric copies.

The human genome contains two highly homologous SMN genes, the SMA pathogenic gene SMN1 and the modifier gene SMN2. These two genes are arranged in tandem on the chromosome, SMN1 is also called SMNT because it is close to the telomere side, and SMN2 is also called SMNC because it is located on the centromere side. The two genes differ by only 5 nucleotide positions (compared to only 2 in the coding region) and encode the same protein. About 95% of SMA patients are caused by homozygous deletion of exon 7 of SMN1 gene, 3% are caused by heterozygous mutations of SMN1 alleles, and the rest are caused by other mutations. SMN2 also has similar functions to SMN1, but its transcripts are usually degraded quickly, and only 10-20% can eventually become functional motor neuron proteins. Therefore, if SMN1 is homozygously deleted, no matter how small the copy number of SMN2 is, it will cause the disease; but the more copies of SMN2, the greater the relative compensation dose, and the disease will be relatively alleviated, and only the mutation of SMN2 will not cause the disease.

status quo

Due to the serious condition of SMA and the high cost of treatment, prenatal diagnosis is still the main preventive method for SMA at this stage. The carrier rate of this disease is high in the population. For ordinary couples, genetic screening for SMA carriers can be carried out before marriage or childbirth, so as to understand the risk of childbearing early and take corresponding intervention measures. For families who have given birth to SMA patients, genetic testing of sick children, as well as genetic counseling and prenatal diagnosis before giving birth again are extremely important; prenatal genetic diagnosis can be used to avoid having children with SMA again.

Rare disease spinal muscular atrophy gene SMN1 molecular diagnostic standard

The detection of SMN1 gene is of great significance to clinical patients. In order to ensure the accuracy of gene detection, Kebai Biotech has launched relevant standard products, which can be selected by manufacturers of kit development.

SMN1 Loss Reference Standard RQP40060

SMN1 p.M200T Reference Standard RQP10560

SMN1 p.Q284Tfs*22 Reference Standard RQP10561

SMN1 p.C123Y Reference Standard RQP10562