Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0700208 (scoliosis)
 8,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increasing number of genomic variations are no more regarded as harmless changes in protein coding sequences or as genetic polymorphisms. Studying the impact of these variations on mRNA metabolism became a central issue to better understand the biological significance of disease. We describe here a severe congenital muscular dystrophy (CMD) with lumbar scoliosis and respiratory complications in a patient, who died at the age of 10. Despite a poor linkage to any form of CMD, total deficiency of laminin-alpha2 rather suggested the occurrence of an MDC1A form. Extensive analysis of LAMA2 gene revealed two novel mutations: a (8007delT) frameshift deletion in exon 57, and a de novo 7nt deletion in intron 17. Using an ex vivo approach, we provided strong evidence that the intron mutation is responsible for complete exon 17 skipping. The mutations are in trans and they each generate a nonsense mRNA potentially elicited to degradation by NMD. We further discuss the impact of mRNA alterations on the subtle phenotypic discrepancies.
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PMID:LAMA2 mRNA processing alterations generate a complete deficiency of laminin-alpha2 protein and a severe congenital muscular dystrophy. 1805 18

Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder characterised by the degeneration of motor neurons and progressive muscle weakness. It is caused by homozygous deletions in the survival motor neuron gene on chromosome 5. SMA shows a wide range of clinical severity, with SMA type I patients often dying before 2 years of age, whereas type III patients experience less severe clinical manifestations and can have a normal life span. Here, we describe the design, setup and utilisation of the TREAT-NMD national SMA patient registries characterised by a small, but fully standardised set of registry items and by genetic confirmation in all patients. We analyse a selection of clinical items from the SMA registries in order to provide a snapshot of the clinical data stratified by SMA subtype, and compare these results with published recommendations on standards of care. Our study included 5,068 SMA patients in 25 countries. A total of 615 patients were ventilated, either invasively (178) or non-invasively (437), 439 received tube feeding and 455 had had scoliosis surgery. Some of these interventions were not available to patients in all countries, but differences were also noted among high-income countries with comparable wealth and health care systems. This study provides the basis for further research, such as quality of life in ventilated SMA patients, and will inform clinical trial planning.
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PMID:Mapping the differences in care for 5,000 spinal muscular atrophy patients, a survey of 24 national registries in North America, Australasia and Europe. 2416 38