Evidence map›Paper›PMID 39920747›Full record

Observational studyOrphanet journal of rare diseases2025

Genomic analysis of the SMN1 gene region in patients with clinically diagnosed spinal muscular atrophy: a retrospective observational study.

Tamaki Kato, Mamoru Yokomura, Yutaka Osawa, Kensuke Matsuo, Yuji Kubo, Taihei Homma, Kayoko Saito

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Orphanet journal of rare diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Biomarkers in spinal muscular atrophy.Frontiers in neurology · 2025
    Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Tamaki KatoInstitute of Medical Genetics, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
Mamoru YokomuraInstitute of Medical Genetics, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
Yutaka OsawaDepartment of Neurology, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Kensuke MatsuoDivision of Pediatrics, Kyoto Tanabe Central Hospital, Kyoto, Japan.
Yuji KuboInstitute of Medical Genetics, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
Taihei HommaBiogen Japan Ltd., Tokyo, Japan.
Kayoko SaitoInstitute of Medical Genetics, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. saito.kayoko@twmu.ac.jp.ORCID http://orcid.org/0000-0003-2632-0873

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSpinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease. Most patients with SMA have a mutation in the survival motor neuron 1 (SMN1) gene on chromosome 5q. With current genetic testing, SMN1 copy number is determined; a diagnosis is reached when the copy number is zero. When the SMN1 copy number is 1, exons and intron/exon boundaries of the allele are examined for single-nucleotide variants (SNVs). Genetically undiagnosed cases of SMA exist when 2 copies of SMN1 exist or when a SNV is in the deep intron. Furthermore, SMN1 is highly homologous to SMN2; therefore, it is expected that many SNVs have not been elucidated.

methodsThis retrospective observational study conducted in Japan used pre-collected DNA samples from patients with clinically diagnosed SMA. Enrollment period was January 28, 2020 to September 30, 2021. SNV analysis of SMN1 (exon 1-8 and intron 1-7) was conducted by long-range polymerase chain reaction and next-generation sequencing.

resultsFrom 336 DNA samples collected from patients, 62 patient samples were included in the SNV analysis. Two patients have been genetically diagnosed (a heterozygous variant in intron 6 with 1 copy of SMN1; a homozygous missense mutation in exon 3 with 2 copies of SMN1). Three SNVs in intron 6, c.834+1506A>G (n = 9), c.834+1751G>A (n = 2), and c.835-367C>A (n = 5) were identified; all were numerically, and c.834+1506A>G and c.835-367C>A were significantly, more frequent in patients with 0 copies versus those with ≥ 1 copy of exon 7 in SMN1. We confirmed 3 hybrid SMN gene types in 5 patients that contained SMN2 gene sequence (aaTgg) flanked by upstream "t" and downstream "G" SMN1 sequence.

conclusionsIn this study of patients with clinically diagnosed SMA, 2 cases with genetic SMN types were identified that would not have been identified through current genetic testing, which examines SMN1 deletions only. Furthermore, for 1 patient with a homozygous SMN1 missense mutation, SMA was not suspected by the current copy number screening method. This study demonstrated the importance of performing full-length sequencing for clinically diagnosed SMA to complement current screening methods.

trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry (Number: UMIN000040095).

Indexed as

Muscular Atrophy, SpinalSurvival of Motor Neuron 1 ProteinChildChild, PreschoolDNA Copy Number VariationsFemaleGenomicsHumansInfantMaleMutationPolymorphism, Single NucleotideRetrospective StudiesSMN1 protein, humanSurvival of Motor Neuron 1 ProteinGenomicsLong-range PCRMutationNext-generation sequencingSingle nucleotide variantSMN1 geneSMN2 geneSpinal muscular atrophy

Identifiers

PMID39920747
PMCPMC11803984

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.