Over the 24-year period, there were 57 spinal muscular atrophy diagnoses in 53 families, and a disease birth prevalence of 1 per 8286 births in Estonia.
A group of researchers in Estonia determined the prevalence of spinal muscular atrophy (SMA) in the country and characterized the epidemiology of the disease to help drive the implementation of SMA screening at birth in Estonia.
The retrospective study analyzed data of patients with SMA referred to a hospital between 1996 and 2020.
Over the 24-year period, there were 57 SMA diagnoses from 53 families, with an SMA birth prevalence of 1 per 8286 births in Estonia. Most patients (43.9%) had SMA type 1, 29.8% had SMA type 3, and 22.8% had SMA type 2, which the researchers said is in line with a previous European report. On average, patients with SMA type 0 (1.8%) were diagnosed at 0.4 months, patients with SMA type 1 were diagnosed at 3.2 months, patients with SMA type 2 were diagnosed at 18.8 months, and patients with SMA type 3 were diagnosed at 13.4 years.
The overwhelming majority (96.5%) of patients had homozygous deletion of SMN1, while 2 patients (3.5%) were compound heterozygous for a deletion of a whole SMN1 gene, including NAIP and GTF2H2 genes, as well as intragenic variant NM_000344.3:c.410dup,p.(Asn137Lysfs*11).
“The identified SMN1 exon 4 variant NM_000344.3:c.410dup, p.(Asn137Lysfs*11) in our study is novel,” researchers said, explaining that it was not present in various databases or published in research from other groups.
“Pathogenicity was classified by the American College of Medical Genetics and Genomics (ACMG) variant interpretation guidelines. By ACMG guidelines, the variant is pathogenic because it is absent in population databases, predicted a null variant, and was detected in trans with the deletion of SMN1 exons 7 and 8,” they noted.
According to the researchers, both of the patients who were compound heterozygotes of SMN1 deletion and a point variant were female, had SMA type 1, and had 2 copies of SMN2. The researchers noted that while the 2 patients shared the same rare variant, they were unable to determine a relationship based on family history within the last 4 to 5 generations.
In total, there were 51 patients who had the SMN2 copy number; the researchers said that the remaining 6 patients were deceased before screening and therefore DNA was unavailable.
“We performed the Multiplex ligation-dependent probe amplification (MPLA) analysis in 51 of the 57 patients to detect the copy number of SMN2 gene, which plays an important role in the disease’s severity,” wrote the researchers. “SMA type 0 patient carried 1 copy of SMN2 which is usual to SMA 0. Our results correlate with the published data, in which 73% of SMA type I patients carry 2 SMN2 copies, 78% of SMA II patients carry 3 copies, 49 and 44% of SMA III patients carry 3 and 4 copies, respectively, and 75% of SMA IV patients have 4 SMN2 copies,” they concluded.
Sarv S, Kahre T, Vaidla E, et al. The birth prevalence of spinal muscular atrophy: a population specific approach in Estonia. Front Genet. Published online December 22, 2021. doi: 10.3389/fgene.2021.796862