Association between the SMN2 gene copy number and clinical characteristics of patients with spinal muscular atrophy with homozygous deletion of exon 7 of the SMN1 gene

Žarkov, Marija; Stojadinović, Aleksandra; Sekulić, Slobodan; Barjaktarović, Iva; Stojiljkovic, Olivera; Perić, Stojan; Keković, Goran; Drašković, Biljana; Stević, Zorica

doi:10.2298/vsp140328072z

Cited by 6 publications

(11 citation statements)

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“…Two other studies examined the relationship between SMA phenotype and SMN2 copy number but did not report the number of patients with three SMN2 copies in different phenotype groups ( 37 , 47 ). Mendonça and colleagues compared patients who were homozygous for an SMN1 deletion with those who were compound heterozygotes ( 47 ).…”

Section: Resultsmentioning

confidence: 99%

“…Zarkov and colleagues reported the mean number of SMN2 copies in patients with SMA type II, III, or IV, and found that the mean number of copies was higher in milder phenotypes (mean 3.1 in type II, 3.7 in type III and 4.2 in type IV; p < 0.05) ( 37 ).…”

Section: Resultsmentioning

confidence: 99%

“…Of the 44 studies, 13 reported on the impact of SMN2 copy number on clinical course/prognosis ( 17 , 21 , 23 , 32 , 36 , 37 , 39 , 42 , 49–51 , 55 , 57 ), of which eight provided data on age at onset and/or mortality ( Table 2 ) ( 21 , 23 , 36 , 49–51 , 55 , 57 ).…”

Section: Resultsmentioning

confidence: 99%

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The impact of three SMN2 gene copies on clinical characteristics and effect of disease-modifying treatment in patients with spinal muscular atrophy: a systematic literature review

Dosi,

Masson

2024

Front. Neurol.

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ObjectiveTo review the clinical characteristics and effect of treatment in patients with spinal muscular atrophy (SMA) and three copies of the SMN2 gene.MethodsWe conducted a literature search in October 2022 to identify English-language clinical research on SMA that included SMN2 copy number according to PRISMA guidelines.ResultsOur search identified 44 studies examining the impact of three SMN2 copies on clinical characteristics (21 on phenotype, 13 on natural history, and 15 on functional status and other signs/symptoms). In children with type I SMA or presymptomatic infants with an SMN1 deletion, three SMN2 copies was associated with later symptom onset, slower decline in motor function and longer survival compared with two SMN2 copies. In patients with SMA type II or III, three SMN2 copies is associated with earlier symptom onset, loss of ambulation, and ventilator dependence compared with four SMN2 copies. Eleven studies examined treatment effects with nusinersen (nine studies), onasemnogene abeparvovec (one study), and a range of treatments (one study) in patients with three SMN2 copies. In presymptomatic infants, early treatment delayed the onset of symptoms and maintained motor function in those with three SMN2 copies. The impact of copy number on treatment response in symptomatic patients is still unclear.ConclusionSMN2 copy number is strongly correlated with SMA phenotype in patients with SMN1 deletion, while no correlation was found in patients with an SMN1 mutation. Patients with three SMN2 copies show a highly variable clinical phenotype. Early initiation of treatment is highly effective in presymptomatic patients with three SMN2 copies.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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The impact of three SMN2 gene copies on clinical characteristics and effect of disease-modifying treatment in patients with spinal muscular atrophy: a systematic literature review

Dosi,

Masson

2024

Front. Neurol.

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“…Gene -NAIP (a neuronal apoptosis inhibitor gene, OMIM: 600355), whose deletions of one or more exons in homozygous state occur in 40-70% of patients with SMA type I 6,7 . In patients with deletion of the 7 and 8 exons of the SMN-gene in a homozygous state, a violation in the NAIP gene is detected simultaneously 8,9,10 . The third gene -H4F5 is located next to the SMN gene.…”

Section: Introductionmentioning

confidence: 99%

Spinal Muscular Atrophy (Werdnig-Hoffmann Atrophy/Disease): Two Case Presentations and Literature Review

Ryznychuk¹,

Kryvchanska²,

Lastivka³

et al. 2018

Arch Balk Med Union

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Atrophie musculaire spinale de Werdnig-Hoffmann: deux rapports de cas et revue de la litterature Introduction. L'atrophie musculaire spinale de type I appartient au groupe des maladies neuromusculaires autosomiques récessives caractérisées par la dégénérescence des cellules des cornes antérieures de la moelle épinière, qui entraîne à son tour une faiblesse musculaire symétrique et une atrophie musculaire. Chez 95% d'enfants, on observe une mortalité précoce jusqu'à l'âge de 2 ans. Rapports de cas. Nous présentons 2 cas cliniques de trouble de Werdnig-Hoffmann chez les enfants de la région de Tchernivtsi, en Ukraine, et faisons une analyse de la littérature sur cette pathologie. Deux cas d'atrophie musculaire sont présentés. Le matériel a été compilé conformément aux normes éthiques applicables aux essais cliniques (Association médicale mondiale, Déclaration d'Helsinki, Principes éthiques pour les recherches médicales humaines). On a utilisé des méthodes généalogiques et moléculaires génétiques, des tests sanguins biochimiques, ENMG. La maladie devrait être suspectée chez les bébés si l'anamnèse indique ABSTRACT Introduction. Spinal muscular atrophy type 1 is an autosomal recessive neuromuscular disorder characterized by degeneration of the anterior horn cells in the spinal cord, leading to symmetric muscle weakness and atrophy. 95% of affected children die before 2 years of age. The annual incidence in the world has been estimated at around 1/11 000. The errors (mutations) in the SMN1 gene prevalence vary from 1: 38 to 1: 70 in the population. The disorder is primarily caused by the homozygous deletions of the gene (5q12.2-q13.3). The SMN gene mutation is primarily caused by a homozygous deletion in exons 7 or 8. Case presentations. 2 clinical cases of children with the Werdnig-Hoffmann disorder will be presented, and a literature review of this pathology. Two cases of spinal muscular atrophy diagnosed in Chernivtsi region, Ukraine, are presented. In both children, a molecular genetic analysis found the homozygous deletions of SMN1 gene in exons 7 and 8. Most affected children die within 2.3-1.3 years of age. These two cases ended lethally due to subinfection. Material was collected in accordance with ethical standards of work person under Helsinki Declaration

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“…These days, the association between SMN2 gene copy number and clinical phenotype in patients with SMA is well known, and its possible effect as a phenotype modifier is being examined. 10 11 Even though SMN2 produces less of the full length protein transcript than SMN1 , it is known the number of SMN2 copies affects the phenotype of SMA. 12 …”

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confidence: 99%

Clinical Characteristics of Spinal Muscular Atrophy in Korea Confirmed by Genetic Analysis

2017

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The objective of this study was to review the clinical characteristics of patients with spinal muscular atrophy and to emphasize the importance of performing genetic mutational analysis at initial patient assessment. This is a single center oriented, retrospective, and descriptive study conducted in Seoul, South Korea. Genetic mutational analysis to detect the deletion of exon 7 of the SMN1 gene on chromosome 5q13 was performed by multiplex ligation-dependent probe amplification. Clinical features, electrodiagnostic study results, muscle biopsy results, and laboratory test results were reviewed from patient medical records. Of all 28 patients (15 males and 13 females), all showed bilateral symmetric proximal dominant weakness. Among them, 3 patients were classified as type I, 14 patients as type II, and 11 patients as type III. Twenty-five patients had scoliosis and eight of these patients received surgical treatment for scoliosis with improvement in clinical outcomes. Ventilator support was used in 15 patients. In terms of the diagnostic process, 15 patients had completed an electrodiagnostic study and muscle biopsy before genetic testing, and six of these patients were initially misdiagnosed with myopathy. Owing to the similar clinical features of SMA and congenital myopathy, an electrodiagnostic study and muscle biopsy could create confusion in the correct diagnosis in some cases. Therefore, it is recommended that genetic mutation analysis should be conducted along with an electrodiagnostic study or muscle biopsy in the diagnostic process for spinal muscular atrophy.

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Association between the SMN2 gene copy number and clinical characteristics of patients with spinal muscular atrophy with homozygous deletion of exon 7 of the SMN1 gene

Abstract: In the Serbian patients with SMA, a higher SMN2 gene copy number correlated with less severe disease phenotype. A possible effect of other phenotype modifiers should not be neglected.

Cited by 6 publications

References 23 publications

The impact of three SMN2 gene copies on clinical characteristics and effect of disease-modifying treatment in patients with spinal muscular atrophy: a systematic literature review

The impact of three SMN2 gene copies on clinical characteristics and effect of disease-modifying treatment in patients with spinal muscular atrophy: a systematic literature review

Spinal Muscular Atrophy (Werdnig-Hoffmann Atrophy/Disease): Two Case Presentations and Literature Review

Clinical Characteristics of Spinal Muscular Atrophy in Korea Confirmed by Genetic Analysis

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