Genetic Modifiers of the Spinal Muscular Atrophy Phenotype

Hryshchenko, N. V.; Yurchenko, A. A.; Karaman, H. S.; Livshits, L. A.

doi:10.3103/s0095452720020073

Cited by 2 publications

(3 citation statements)

References 27 publications

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“…A statistically significant effect of SMN2 copy number on SMA phenotype was reported in all but one of the 12 studies that undertook statistical analysis ( 6 , 15 , 16 , 19 , 22 , 33 , 35–37 , 40 , 46 , 55 ). Excluding the study by Wijaya and colleagues ( 52 ), the studies reported that three SMN2 copies were present in between 0 and 57.1% of patients with SMA type I, 20.4%–100.0% of patients with SMA type II, 15.2%–77.8% of those with SMA type III, and 0%–33.3% of those with SMA type IV ( Table 1 ).…”

Section: Resultsmentioning

confidence: 94%

“…Of the 44 studies, 21 assessed the relationship between SMN2 copy number and SMA phenotype, and 19/21 studies reported the number of patients with three SMN2 copies within each phenotype group ( Table 1 ) ( 6 , 15 , 16 , 18 , 19 , 22 , 24 , 30 , 33 , 35 , 36 , 38 , 40–42 , 46 , 50 , 52 , 55 ).…”

Section: Resultsmentioning

confidence: 99%

“…Several studies, including the one by De Sanctis and colleagues described above, noted discordance between SMN2 copy number and expected clinical phenotype. Lusakowska and colleagues reported that 85/140 patients with type I SMA (60.7%) in the Polish SMA registry had three or more SMN2 copies ( 50 ); the cohort of 285 Dutch patients reported by Wadman and colleagues contained 30 patients with type I SMA who had three or more copies of SMN2 ( 6 ); and Hryshchenko and colleagues found three SMN2 copies in two patients with the most severe form of SMA (type 0) ( 46 ). In fact, Wadman and colleagues noted that phenotype was most variable among patients with three SMN2 copies, ranging from those unable to sit independently (type Ic) to ambulant patients (type IIIa) ( 6 ).…”

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: 94%

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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The First Report of Iranian Registry of Patients with Spinal Muscular Atrophy

Mansouri

Heidari

Bemanalizadeh

et al. 2023

JND

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Background: insufficient amounts of survival motor neuron protein is leading to one of the most disabling neuromuscular diseases, spinal muscular atrophy (SMA). Before the current study, the detailed characteristics of Iranian patients with SMA had not been determined. Objective: To describe the key demographic, clinical, and genetic characteristics of patients with SMA registered in the Iranian Registry of SMA (IRSMA). Methods: IRSMA has been established since 2018, and the demographic, clinical, and genetic characteristics of patients with SMA were recorded according to the methods of treat neuromuscular disease (TREAT-NMD) project. Results: By October 1, 2022, 781 patients with 5q SMA were registered. Of them, 164 patients died, the majority of them had SMA type 1 and died during the first 20 months of life. The median survival of patients with type 1 SMA was 23 months. The consanguinity rate in 617 alive patients was 52.4%, while merely 24.8% of them had a positive family history. The most common type of SMA in live patients was type 3. Morbidities were defined as having scoliosis (44.1%), wheelchair dependency (36.8%), tube feeding (8.1%), and requiring mechanical ventilation (9.9%). Most of the registered patients had a homozygous deletion of SMN1, while the frequency of patients with higher copy numbers of SMN2, was less in more severe types of the disease. Earlier onset of the disease was significantly seen in patients with a homozygous deletion of SMN1. The neuronal apoptosis inhibitory protein (NAIP) gene deletion was associated with a higher incidence of more severe types of SMA, higher dependency on ventilators, tube feeding, and earlier onset of the disease. Conclusions: The IRSMA is the first established Iranian nationwide registry of patients with SMA. Using this registry, decision-makers, researchers, and practitioners can precisely understand the epidemiology, characteristics, and genetics of patients with SMA in Iran.

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Genetic Modifiers of the Spinal Muscular Atrophy Phenotype

Cited by 2 publications

References 27 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

The First Report of Iranian Registry of Patients with Spinal Muscular Atrophy

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