Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q16637 (SMA)
 8,107 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease with an autosomal recessive trait of inheritance and great variability of its clinical course - from the lethal congenital type (SMA0) to the adult-onset form (SMA4). The disease is associated with a deficiency of SMN protein, which is encoded by two genes SMN1 and SMN2. Clinical symptoms depend on mutations in the SMN1 gene. The number of copies of twin similar SMN2 gene, which produces small amounts of SMN protein, is the main phenotype modifier, which determines the clinical severity of the disease. Until recently, it was considered that spinal cord motoneurons undergo selective loss. Recent studies have shown the role of SMN protein in various cellular processes and the multisystemic character of SMA. The aim of the therapeutic strategies developed so far has been to increase the expression of SMN protein by modifying the splicing of SMN2 gene (intrathecally administered antisense oligonucleotide - nusinersen; orally available small molecules: RG7916 and LMI070 or SMN1 gene replacement therapy (AAV9-SMN). The first SMN2-directed antisense oligonucleotide (nusinersen) has demonstrated in clinical trials high efficiency, and it has now been registered. The best effects were obtained in patients who were introduced to the drug in the pre symptomatic period. Studies on other substances are ongoing. The great advances in SMA therapy and increased understanding of the pathogenesis of the disease raise hopes for changes to the natural history of the disease. Simultaneously, it increases awareness of the need to improve the standard of patient care and early diagnosis (newborn screening). Many questions (e.g. emerging phenotypes, combined therapies, systemic vs. intrathecal administration, long-term consequences, and complications of the therapy) will require further studies and observations.
 ...
PMID:Spinal muscular atrophy - new therapies, new challenges. 3192 83

Spinal muscular atrophy (SMA) is a type of autosomal recessive genetic disease, which seriously threatens the health and lives of children and adolescents. We attempted to find some genes and mutations related to the onset of SMA. Eighty-three whole-blood samples were collected from 28 core families, including 28 probands with clinically suspected SMA (20 SMA patients, 5 non-SMA children, and 3 patients with unknown etiology) and their parents. The multiplex ligation probe amplification (MLPA) was performed for preliminary diagnosis. The high-throughput sequencing technology was used to conduct the whole-exome sequencing analysis. We analyzed the mutations in adjacent genes of SMN1 gene and the unique mutations that only occurred in SMA patients. According to the MLPA results, 20 probands were regarded as experimental group and 5 non-SMA children as control group. A total of 10 mutations were identified in the adjacent genes of SMN1 gene. GUSBP1 g.[69515863G>A], GUSBP1 g.[69515870C>T], and SMA4 g.[69515738C>A] were the top three most frequent sites. SMA4 g.[69515726A>G] and OCLN c.[818G>T] have not been reported in the existing relevant researches. Seventeen point mutations in the DYNC1H1 gene were only recognized in SMA children, and the top two most common mutations were c.[2869-34A>T] and c.[345-89A>G]; c.[7473+105C>T] was the splicing mutation that might change the mRNA splicing site. The mutations of SMA4 g.[69515726A>G], OCLN c.[818G>T], DYNC1H1 c.[2869-34A>T], DYNC1H1 c.[345-89A>G], and DYNC1H1 c.[7473+105C>T] in the adjacent genes of SMN1 gene and other genes might be related to the onset of SMA.
 ...
PMID:Discovery of specific mutations in spinal muscular atrophy patients by next-generation sequencing. 3289 76