scholarly journals Exome reanalysis and proteomic profiling identified TRIP4 as a novel cause of cerebellar hypoplasia and spinal muscular atrophy (PCH1)

2021 ◽  
Author(s):  
Ana Töpf ◽  
◽  
Angela Pyle ◽  
Helen Griffin ◽  
Leslie Matalonga ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Rna Processing ◽  
Bone Fractures ◽  
Muscular Atrophy ◽  
Congenital Muscular Dystrophy ◽  
Severe Form ◽  
Sequencing Analysis ◽  
Cerebellar Hypoplasia ◽  
Proteomic Profiling ◽  
Transcriptional Coregulator

AbstractTRIP4 is one of the subunits of the transcriptional coregulator ASC-1, a ribonucleoprotein complex that participates in transcriptional coactivation and RNA processing events. Recessive variants in the TRIP4 gene have been associated with spinal muscular atrophy with bone fractures as well as a severe form of congenital muscular dystrophy. Here we present the diagnostic journey of a patient with cerebellar hypoplasia and spinal muscular atrophy (PCH1) and congenital bone fractures. Initial exome sequencing analysis revealed no candidate variants. Reanalysis of the exome data by inclusion in the Solve-RD project resulted in the identification of a homozygous stop-gain variant in the TRIP4 gene, previously reported as disease-causing. This highlights the importance of analysis reiteration and improved and updated bioinformatic pipelines. Proteomic profile of the patient’s fibroblasts showed altered RNA-processing and impaired exosome activity supporting the pathogenicity of the detected variant. In addition, we identified a novel genetic form of PCH1, further strengthening the link of this characteristic phenotype with altered RNA metabolism.

scholarly journals Mutations in Subunits of the Activating Signal Cointegrator 1 Complex Are Associated with Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures

2016 ◽  
Vol 98 (3) ◽  
pp. 473-489 ◽  
Author(s):  
Ellen Knierim ◽  
Hiromi Hirata ◽  
Nicole I. Wolf ◽  
Susanne Morales-Gonzalez ◽  
Gudrun Schottmann ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Bone Fractures ◽  
Muscular Atrophy

scholarly journals Cerebrospinal fluid proteomic profiling in nusinersen‐treated patients with spinal muscular atrophy

2020 ◽  
Vol 153 (5) ◽  
pp. 650-661 ◽  
Author(s):  
Tobias Kessler ◽  
Pauline Latzer ◽  
Dominic Schmid ◽  
Uwe Warnken ◽  
Afshin Saffari ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Proteomic Profiling

Neonatal spinal muscular atrophy with multiple contractures, bone fractures, respiratory insufficiency and 5q13 deletion

2004 ◽  
Vol 107 (5) ◽  
pp. 475-478 ◽  
Author(s):  
M. A. Garc�a-Cabezas ◽  
A. Garc�a-Alix ◽  
Y. Mart�n ◽  
M. Guti�rrez ◽  
C. Hern�ndez ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Respiratory Insufficiency ◽  
Bone Fractures ◽  
Muscular Atrophy

scholarly journals Growth patterns in children with spinal muscular atrophy

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ramona De Amicis ◽  
Giovanni Baranello ◽  
Andrea Foppiani ◽  
Alessandro Leone ◽  
Alberto Battezzati ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Neuromuscular Disorder ◽  
Severe Form ◽  
Growth Patterns ◽  
Standards Of Care ◽  
Growth Standards ◽  
Treatment Naïve

Abstract Background Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by muscle atrophy and weakness. SMA type 1 (SMA1) is the most severe form: affected infants are unable to sit unaided; SMA type 2 (SMA2) children can sit, but are not able to walk independently. The Standards of Care has improved quality of life and the increasing availability of disease-modifying treatments is progressively changing the natural history; so, the clinical assessment of nutritional status has become even more crucial. Aims of this multicenter study were to present the growth pattern of treatment-naïve SMA1 and SMA2, and to compare it with the general growth standards. Results Body Weight (BW, kg) and Supine Length (SL, cm) were collected using a published standardized procedure. SMA-specific growth percentiles curves were developed and compared to the WHO reference data. We recruited 133 SMA1 and 82 SMA2 (48.8% females). Mean ages were 0.6 (0.4–1.6) and 4.1 (2.1–6.7) years, respectively. We present here a set of disease-specific percentiles curves of BW, SL, and BMI-for-age for girls and boys with SMA1 and SMA2. These curves show that BW is significantly lower in SMA than healthy peers, while SL is more variable. BMI is also typically lower in both sexes and at all ages. Conclusions These data on treatment-naïve patients point toward a better understanding of growth in SMA and could be useful to improve the clinical management and to assess the efficacy of the available and forthcoming therapies not only on motor function, but also on growth.

scholarly journals Review of respiratory therapies in patients with spinal muscular atrophy

2018 ◽  
Vol 1 (1) ◽  
pp. 10-17
Author(s):  
V. Yu. Artemenko ◽  
E. V. Plotna
Keyword(s):  
Respiratory Failure ◽  
Spinal Muscular Atrophy ◽  
Motor Neurons ◽  
Sleep Disturbances ◽  
Muscular Atrophy ◽  
Neuromuscular Diseases ◽  
Respiratory Muscles ◽  
Autosomal Recessive Inheritance ◽  
Severe Form ◽  
State Of Rest

The purpose of this article was to systematize available literary data and to provide general recommendations for respiratory therapy in patients with spinal muscular atrophy. Spinal muscular atrophy (SMA) is a severe neuromuscular disease with autosomal recessive inheritance with degeneration of alpha motor neurons in the anterior horns of the spinal cord, leading to progressive proximal muscle weakness and paralysis. SMN 1–2 genes potentially encode identical proteins, although most of the transcripts of the SMN1 genes are halfsized, whereas most transcripts of the SMN2 genes do not contain the seventh exon. Therefore, the SMN2 gene is only partially functional, and a low-level SMN protein is produced in SMA patients. Moreover, the number of copies of the SMN2 can not be considered an exact predictive factor for any particular patient. The main causes of mortality and deterioration in the quality of life are the development of secondary respiratory failure. Type 1 (a, b, c) is the heaviest: early onset and lack of motor abilities, usually patients with a disease of this type survive no more than 2 years. Type 2 – an intermediate type characterized by a later onset, the patient may take a sedentary position, survival may reach the adult height. Type 3 is the softest form that manifests itself at the age of 1 year, the patient can walk and stand. The forecast is more favorable. Type 4 “adult form” manifests itself at the age from 10 to 20 or from 20 to 30 years and has a favorable outlook. The main causes of respiratory failure in patients with neuromuscular diseases are weakness of the respiratory muscles, unproductive cough and sleep disturbances. The weakness of the respiratory muscles, defined as the inability of resting respiratory muscles in the state of rest to create a normal level of pressure and air flow velocity when entering and exhaling, is common. Patients with neuromuscular diseases are susceptible to sleep disruption, especially in the REM sleep phase, with the most frequent form of this disorder being hypoventilation. Over time, hypoventilation in a dream can become more prolonged, resulting in the development of a severe form of hypoxia, an increase in the level of carbon dioxide in the blood and the suppression of the activity of the respiratory center. Thus, as a result of the review of literary data, a strategy of respiratory support in patients with CMA was proposed.

Tracheotomy and children with spinal muscular atrophy type 1

2012 ◽  
Vol 19 (3) ◽  
pp. 408-418 ◽  
Author(s):  
Brigitte Rul ◽  
Franco Carnevale ◽  
Brigitte Estournet ◽  
Michèle Rudler ◽  
Christian Hervé
Keyword(s):  
Mechanical Ventilation ◽  
Spinal Muscular Atrophy ◽  
Motor Neurons ◽  
Muscular Atrophy ◽  
Severe Form ◽  
First Year ◽  
Spinal Muscular Atrophy Type ◽  
Intellectual Capacity ◽  
First Year Of Life

Spinal muscular atrophy (SMA) type 1 is a genetic neuromuscular disease in children that leads to degeneration of spinal cord motor neurons. This sometimes results in severe muscular paralysis requiring mechanical ventilation to sustain the child’s life. The onset of SMA type 1, the most severe form of the disease, is during the first year of life. These children become severely paralysed, but retain their intellectual capacity. Ethical concerns arise when mechanical ventilation becomes necessary for survival. When professionals assess the resulting life for the child and family, they sometimes fear it will result in unreasonably excessive care. The aim of this article is to present an analysis of ethical arguments that could support or oppose the provision of invasive ventilation in this population. This examination is particularly relevant as France is one of the few countries performing tracheotomies and mechanical ventilation for this condition.

scholarly journals Air stacking: effects on pulmonary function in patients with spinal muscular atrophy and in patients with congenital muscular dystrophy,

2014 ◽  
Vol 40 (5) ◽  
pp. 528-534 ◽  
Author(s):  
Tanyse Bahia Carvalho Marques ◽  
Juliana de Carvalho Neves ◽  
Leslie Andrews Portes ◽  
João Marcos Salge ◽  
Edmar Zanoteli ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Pulmonary Function ◽  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Pulmonary Function Tests ◽  
Congenital Muscular Dystrophy ◽  
Spinal Deformities ◽  
Respiratory Complications ◽  
Function Tests ◽  
Before And After

OBJECTIVE: Respiratory complications are the main causes of morbidity and mortality in patients with neuromuscular disease (NMD). The objectives of this study were to determine the effects that routine daily home air-stacking maneuvers have on pulmonary function in patients with spinal muscular atrophy (SMA) and in patients with congenital muscular dystrophy (CMD), as well as to identify associations between spinal deformities and the effects of the maneuvers. METHODS: Eighteen NMD patients (ten with CMD and eight with SMA) were submitted to routine daily air-stacking maneuvers at home with manual resuscitators for four to six months, undergoing pulmonary function tests before and after that period. The pulmonary function tests included measurements of FVC; PEF; maximum insufflation capacity (MIC); and assisted and unassisted peak cough flow (APCF and UPCF, respectively) with insufflations. RESULTS: After the use of home air-stacking maneuvers, there were improvements in the APCF and UPCF. In the patients without scoliosis, there was also a significant increase in FVC. When comparing patients with and without scoliosis, the increases in APCF and UPCF were more pronounced in those without scoliosis. CONCLUSIONS: Routine daily air-stacking maneuvers with a manual resuscitator appear to increase UPCF and APCF in patients with NMD, especially in those without scoliosis.

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