scholarly journals Clinical and molecular analysis of spinal muscular atrophy in Brazilian patients

1999 ◽  
Vol 22 (4) ◽  
pp. 487-492 ◽  
Author(s):  
C.A. Kim ◽  
M.R. Passos-Bueno ◽  
S.K. Marie ◽  
A. Cerqueira ◽  
U. Conti ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Disease Type ◽  
Survival Motor Neuron ◽  
Type I ◽  
Type Ii ◽  
Inhibitory Protein ◽  
Type Iii ◽  
Smn Gene ◽  
Naip Gene

Spinal muscular atrophy (SMA), the second most common lethal autosomal recessive disorder, has an incidence of 1:10,000 newborns. SMA is divided into acute (Werdnig-Hoffmann disease, type I), intermediate (type II) and juvenile forms (Kugelberg-Welander disease, type III). The gene of all three forms of SMA maps to chromosome 5q 11.2-13.3. Two candidate genes, the survival motor neuron (SMN) gene and the neuronal apoptosis inhibitory protein (NAIP) gene, have been identified; SMN is deleted in most SMA patients. We studied both genes in 87 Brazilian SMA patients (20 type I, 14 type II and 53 type III) from 74 unrelated families, by using PCR and single strand conformation polymorphism (SSCP). Deletions of exons 7 and/or 8 of the SMN gene were found in 69% of the families: 16/20 in type I, 9/12 in type II and 26/42 in type III. Among 51 families with deletions, 44 had both exons deleted while seven had deletions only of exon 7. Deletions of exon 5 of the NAIP gene were found in 7/20 of type I, 2/12 of type II and 1/42 of type III patients. No deletion of SMN and NAIP genes was found in 112 parents, 26 unaffected sibs and 104 normal controls. No correlation between deletions of one or both genes and phenotype severity was found.

scholarly journals Application of DNA-based tests for diagnosis of spinal muscular atrophy in Saudi Arabia

1999 ◽  
Vol 5 (6) ◽  
pp. 1225-1229
Author(s):  
S. Al Rajeh ◽  
R. Majumdar ◽  
A. Awada ◽  
M. Al Jumah
Keyword(s):  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Survival Motor Neuron ◽  
Type I ◽  
Type Ii ◽  
Inhibitory Protein ◽  
Neuronal Apoptosis Inhibitory Protein ◽  
Smn Gene ◽  
Naip Gene ◽  
Homozygous Deletions

We examined the deletion of the survival motor neuron [SMN] and neuronal apoptosis inhibitory protein [NAIP]genes in patients with spinal muscular atrophy [SMA] using polymerase chain reaction followed by restriction site assay methods. The study included 16 Saudi patients [9 SMA type I and 7 SMA type II]and 6 healthy Saudi volunteers. The homozygous deletions of exons 7 and 8 of the telomeric SMN gene, and exon 5 of the NAIP gene were found in all SMA type I patients. Exons 7 and 8 of telomeric SMN were deleted in all SMA type II patients. However, exon 5 of NAIP was deleted in three of the seven cases. All control volunteers and all family members of the patients had normal SMN and NAIP. The incidence of NAIP deletion was higher in the more severe SMA cases and the dual deletion of the SMN and NAIP genes was more common in Saudi SMA type I patients compared with patients of other ethnic groups

scholarly journals Molecular Analysis of Survival Motor Neuron and Neuronal Apoptosis Inhibitory Protein Genes in Macedonian Spinal Muscular Atrophy Patients

2007 ◽  
Vol 10 (2) ◽  
pp. 55-60 ◽  
Author(s):  
S Kocheva ◽  
S Vlaski-Jekic ◽  
M Kuturec ◽  
G Efremov
Keyword(s):  
Motor Neuron ◽  
Neuronal Apoptosis ◽  
Muscular Atrophy ◽  
Survival Motor Neuron ◽  
Type I ◽  
Type Ii ◽  
Inhibitory Protein ◽  
Neuronal Apoptosis Inhibitory Protein ◽  
Smn Gene ◽  
Naip Gene

Molecular Analysis of Survival Motor Neuron and Neuronal Apoptosis Inhibitory Protein Genes in Macedonian Spinal Muscular Atrophy PatientsSpinal muscular atrophy (SMA) is classified according to the age of onset and severity of the clinical manifestations into: acute (Werding-Hoffman disease or type I), intermediate (type II) and juvenile (Kugelberg-Wilander disease or type III) forms. All three SMAs have been linked to markers at 5q11.2-q13.3. Two candidate genes deleted in SMA patients are the survival motor neuron (SMN) gene and the neuronal apoptosis inhibitory protein (NAIP) gene. We have performed molecular analyses of these genes in 30 unrelated Macedonian families (17 with type I, eight with type II and five with type III forms of the disease). Deletions of exons 7 and 8 of the SMN gene were found in 76.6% (23/30) of patients (94.1% in type I, 87.5% in type II). Among these 23 families, 19 had both exons deleted, while four had deletions only of exon 7. Deletions of exon 5 of the NAIP gene were found in 41.2% (7/17) patients with type I SMA and in 12.5% (1/8) of patients with type II SMA. No deletions of the SMN gene were found in 30 parents and 30 normal controls. We found 2/30 (6.7%) parents to be homozygous for the deletion of exon 5. Our data support the hypothesis that the telomeric SMN gene plays a major role in determining the clinical course of the disease, while the defects in the NAIP gene have only a modifying effect on the phenotype.

scholarly journals Clinical and Genetic Study of Algerian Patients with Spinal Muscular Atrophy

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Y. Sifi ◽  
K. Sifi ◽  
A. Boulefkhad ◽  
N. Abadi ◽  
Z. Bouderda ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Disease Type ◽  
Intermediate Form ◽  
Type I ◽  
Type Ii ◽  
Type Iii ◽  
Type Iv ◽  
Form Type ◽  
Homozygous Deletions

Spinal muscular atrophy (SMA) is the second most common lethal autosomal recessive disorder. It is divided into the acute Werdnig-Hoffmann disease (type I), the intermediate form (type II), the Kugelberg-Welander disease (type III), and the adult form (type IV). The gene involved in all four forms of SMA, the so-called survival motor neuron (SMN) gene, is duplicated, with a telomeric (tel SMN or SMN1) and a centromeric copy (cent SMN or SMN2). SMN1 is homozygously deleted in over 95% of SMA patients. Another candidate gene in SMA is the neuronal apoptosis inhibitory protein (NAIP) gene; it shows homozygous deletions in 45–67% of type I and 20–42% of type II/type III patients. Here we studied the SMN and NAIP genes in 92 Algerian SMA patients (20 type I, 16 type II, 53 type III, and 3 type IV) from 57 unrelated families, using a semiquantitative PCR approach. Homozygous deletions of SMN1 exons 7 and/or 8 were found in 75% of the families. Deletions of exon 4 and/or 5 of the NAIP gene were found in around 25%. Conversely, the quantitative analysis of SMN2 copies showed a significant correlation between SMN2 copy number and the type of SMA.

scholarly journals Quality of life of  children with spinal muscular atrophy  and their caregivers  from the perspective of caregivers :  a Chinese cross-sectional study

2020 ◽  
Author(s):  
Mei Yao ◽  
Ying Ma ◽  
Ruiying Qian ◽  
Yu Xia ◽  
Changzheng Yuan ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Muscular Atrophy ◽  
Cross Sectional Study ◽  
Type I ◽  
Type Ii ◽  
Cross Sectional ◽  
Type Iii ◽  
Quality Of Life Inventory ◽  
Life Inventory

Abstract Background: Spinal muscular atrophy (SMA) is an autosomal-recessive motor neuron disease leading to dysfunction of multiple organs. SMA can impair the quality of life (QoL) of patients and family. We aimed to evaluate the QoL of children with SMA and their caregivers and to identify the factors associated with QoL in a cross-sectional study conducted in China.Methods: We recruited 101 children aged 0-17 years with SMA and their caregivers from a children’s hospital in China. Twenty-six children had type I SMA, 56 type II and 19 type III. Each child’s QoL was measured by the Pediatric Quality of Life Inventory 3.0 Neuromuscular Module (PedsQL NMM), which was completed by the child’s caregivers. The caregiver’s QoL was measured by the Pediatric Quality of Life Inventory Family Impact Module (PedsQL FIM). Information on sociodemographic characteristics, disease-specific characteristics, and treatments were collected using the proxy-reported questionnaire. Two-sample t-tests and one-way ANOVA were used to compare differences in average scores of QoL across subgroups.Results: Children with type III SMA had a higher average Total score of PedsQL NMM and higher average scores in domains Neuromuscular disease and Family resources than children with type I or type II SMA (p < 0.001). Caregivers of children with type III SMA reported higher average scores in the domains of Physical, Emotional, Social, and Cognitive functioning of the PedsQL FIM than those of children with types I or II SMA (p < 0.05). In addition, disease-related characteristics (e.g. limited mobility, stable course of disease, skeleton deformity, and digestive system dysfunction) and respiratory support were associated with lower average scores of PedsQL NMM and PedsQL FIM (p < 0.05). Exercise training, multidisciplinary team management and use of the medication Nusinersen were each associated with higher average scores in both PedsQL NMM and FIM (p < 0.05). Conclusion: Our study has demonstrated factors that may impair or improve QoL of children patients with SMA and their parents. Particularly, QoL was relatively poor in children with type I and type II SMA as well as in their caregivers compared to those with type III SMA. We strongly recommend that standard of care in a multidisciplinary team (MDT) be strengthened to improve the QoL of SMA patients. Our study called for increased attention from clinical physicians on measuring QoL in their clinical practices in order to enhance the understanding of impacts of SMA and to make better decisions regarding treatment.

scholarly journals Nusinersen in later-onset spinal muscular atrophy

Neurology ◽  
2019 ◽  
Vol 92 (21) ◽  
pp. e2492-e2506 ◽  
Author(s):  
Basil T. Darras ◽  
Claudia A. Chiriboga ◽  
Susan T. Iannaccone ◽  
Kathryn J. Swoboda ◽  
Jacqueline Montes ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Motor Function ◽  
Muscular Atrophy ◽  
Compound Muscle Action Potential ◽  
Extension Study ◽  
Type Ii ◽  
Open Label ◽  
Type Iii ◽  
Link Type ◽  
Phase 1B

ObjectiveTo report results of intrathecal nusinersen in children with later-onset spinal muscular atrophy (SMA).MethodsAnalyses included children from a phase 1b/2a study (ISIS-396443-CS2; NCT01703988) who first received nusinersen during that study and were eligible to continue treatment in the extension study (ISIS-396443-CS12; NCT02052791). The phase 1b/2a study was a 253-day, ascending dose (3, 6, 9, 12 mg), multiple-dose, open-label, multicenter study that enrolled children with SMA aged 2–15 years. The extension study was a 715-day, single-dose level (12 mg) study. Time between studies varied by participant (196–413 days). Assessments included the Hammersmith Functional Motor Scale–Expanded (HFMSE), Upper Limb Module (ULM), 6-Minute Walk Test (6MWT), compound muscle action potential (CMAP), and quantitative multipoint incremental motor unit number estimation. Safety also was assessed.ResultsTwenty-eight children were included (SMA type II, n = 11; SMA type III, n = 17). Mean HFMSE scores, ULM scores, and 6MWT distances improved by the day 1,150 visit (HFMSE: SMA type II, +10.8 points; SMA type III, +1.8 points; ULM: SMA type II, +4.0 points; 6MWT: SMA type III, +92.0 meters). Mean CMAP values remained relatively stable. No children discontinued treatment due to adverse events.ConclusionsNusinersen treatment over ∼3 years resulted in motor function improvements and disease activity stabilization not observed in natural history cohorts. These results document the long-term benefit of nusinersen in later-onset SMA, including SMA type III.Clinicaltrials.gov identifierNCT01703988 (ISIS-396443-CS2); NCT02052791 (ISIS-396443-CS12).Classification of evidenceThis study provides Class IV evidence that nusinersen improves motor function in children with later-onset SMA.

Disease impact on general well-being and therapeutic expectations of European Type II and Type III spinal muscular atrophy patients

2017 ◽  
Vol 27 (5) ◽  
pp. 428-438 ◽  
Author(s):  
Françoise Rouault ◽  
Vanessa Christie-Brown ◽  
Ria Broekgaarden ◽  
Nicole Gusset ◽  
Doug Henderson ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Well Being ◽  
Type Ii ◽  
Type Iii ◽  
Disease Impact

scholarly journals Quality of life of  children with spinal muscular atrophy  and their caregivers  from the perspective of caregivers :  a Chinese cross-sectional study

2020 ◽  
Author(s):  
Mei Yao ◽  
Ying Ma ◽  
Ruiying Qian ◽  
Yu Xia ◽  
Changzheng Yuan ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Muscular Atrophy ◽  
Cross Sectional Study ◽  
Type I ◽  
Type Ii ◽  
Cross Sectional ◽  
Type Iii ◽  
Quality Of Life Inventory ◽  
Life Inventory

Abstract Background: Spinal muscular atrophy (SMA) is an autosomal-recessive motor neuron disease leading to dysfunction of multiple organs. SMA can impair the quality of life (QoL) of patients and family. We aimed to evaluate the QoL of children with SMA and their caregivers and to identify the factors associated with QoL in a cross-sectional study conducted in China.Methods: We recruited 101 children aged 0-17 years with SMA and their caregivers from a children’s hospital in China. Twenty-six children had type I SMA, 56 type II and 19 type III. Each child’s QoL was measured by the Pediatric Quality of Life Inventory 3.0 Neuromuscular Module (PedsQL NMM), which was completed by the child’s caregivers. The caregiver’s QoL was measured by the Pediatric Quality of Life Inventory Family Impact Module (PedsQL FIM). Information on sociodemographic characteristics, disease-specific characteristics, and treatments were collected using the proxy-reported questionnaire. Two-sample t-tests and one-way ANOVA were used to compare differences in average scores of QoL across subgroups.Results: Children with type III SMA had a higher average Total score of PedsQL NMM and higher average scores in domains Neuromuscular disease and Family resources than children with type I or type II SMA (p < 0.001). Caregivers of children with type III SMA reported higher average scores in the domains of Physical, Emotional, Social, and Cognitive functioning of the PedsQL FIM than those of children with types I or II SMA (p < 0.05). In addition, disease-related characteristics (e.g. limited mobility, motor degeneration, skeleton deformity, and digestive system dysfunction) and respiratory support were associated with lower average scores of PedsQL NMM and PedsQL FIM (p < 0.05). Exercise training, multidisciplinary team management and use of the medication Nusinersen were each associated with higher average scores in both PedsQL NMM and FIM (p < 0.05).Conclusion: Our study has demonstrated factors that may impair or improve QoL of children patients with SMA and their parents. Particularly, QoL was relatively poor in children with type I and type II SMA as well as in their caregivers compared to those with type III SMA. We strongly recommend that standard of care in a multidisciplinary team (MDT) be strengthened to improve the QoL of SMA patients. Our study called for increased attention from clinical physicians on measuring QoL in their clinical practices in order to enhance the understanding of impacts of SMA and to make better decisions regarding treatment.

Sign in / Sign up

Export Citation Format

Share Document