Genotype Structure Alterations in 5q SMA Patients as a Result of the Newborn Screening Program Implementation in the Russian Federation

Abstract

Since 2023, the Russian Federation (RF) has implemented an expanded newborn screening (NBS) program for 36 hereditary disorders, which now includes 5q spinal muscular atrophy (5q SMA). As a result of newborn screening for 5q SMA conducted in the RF during 2023-2024, 288 newborns with a homozygous deletion of exon 7 in the SMN1 gene were identified by molecular genetic methods. The overall observed incidence of 5q SMA was 1 in 8439 newborns, which does not significantly differ from the expected incidence of 1 in 7953 newborns, established by previous pilot screening projects (p > 0.05). A comparison of the genotypes of patients identified through selective and newborn screening showed statistically significant differences in the proportions of patients carrying two, three, and four or more copies of the SMN2 gene. These findings demonstrate that the NBS program is effective in detecting both individuals with more severe phenotypes, as expected, and those with milder forms of the disease.

Keywords: 5q SMA; SMN1 exon 7 deletion; genotype; newborn screening; number of SMN2 exon 7 copies; selective screening; spinal muscular atrophy 5q.

Figure 1

Distribution of SMN2 exon 7 copy numbers: (a) Distribution of SMN2 exon 7 copy numbers among 490 patients with a homozygous deletion of SMN1 exon 7, identified through selective 5q SMA screening prior to the launch of pilot projects and newborn screening in 2020–2021 (Selective Screening Group 1, SS2020–2021); (b) distribution of SMN2 exon 7 copy numbers among 288 newborns with a homozygous deletion of SMN1 exon 7, identified through newborn screening in 2023–2024 (NBS2023–2024); (c) distribution of SMN2 exon 7 copy numbers among 140 patients with a homozygous deletion of SMN1 exon 7, identified through selective 5q SMA screening during the implementation of newborn screening in 2023 (Selective Screening Group 2, SS2023); (d) distribution of SMN2 exon 7 copy numbers among 86 patients with a homozygous deletion of SMN1 exon 7, identified through selective 5q SMA screening during the implementation of newborn screening in 2024 (Selective Screening Group 3, SS2024).

Figure 2

Histogram of the age distribution at the time of application among 490 patients in 2020–2021 (Group 1, SS2020–2021), 140 patients screened in 2023 (Group 2, SS2023), and 86 patients in 2024 (Group 3, SS2024), shown as percentages, all with a confirmed diagnosis of 5q SMA through the selective screening program.

Figure 3

Histogram of genotype distribution across all selective screening (SS) groups and newborn screening (NBS) groups by year, along with the results of pairwise statistical comparisons using the χ2 test with Bonferroni correction.

Figure 4

Histogram of genotype proportions across all three selective screening (SS) groups and the newborn screening (NBS) group, categorized by the number of SMN2 gene copies and the presence of a hybrid gene.

Figure 5

The block diagram of the three selective screening groups included in the study: Selective Screening Prior to Nationwide Screening Projects, SS2020–2021, Selective Screening During NBS in 2023, SS2023, Selective Screening During NBS in 2024, SS2024; and the selective screening group excluded from the study—SS2022.