Variability in pathogenicity prediction programs: impact on clinical diagnostics

The performance of 17 publicly available pathogenicity prediction programs was assayed using a dataset consisting of 122 credibly pathogenic and benign variants in genes associated with the RASopathy family of disorders and limb ‐girdle muscular dystrophy. Performance metrics were compared between the programs to determine the most accurate program for loss of function and gain‐of‐function mechanisms. The best performer was MutPred, which had a weighted accuracy of 82.6% in the full dataset. AbstractCurrent practice by clinical diagnostic laboratories is to utilize online prediction programs to help determine the significance of novel variants in a given gene sequence. However, these programs vary widely in their methods and ability to correctly predict the pathogenicity of a given sequence change. The performance of 17 publicly available pathogenicity prediction programs was assayed using a dataset consisting of 122 credibly pathogenic and benign variants in genes associated with the RASopathy family of disorders and limb ‐girdle muscular dystrophy. Performance metrics were compared between the programs to determine the most accurate program for loss‐of‐function and gain‐of‐function mechanisms. No one program correctly predicted the pathogenicity of all variants analyzed. A major hindrance to the analysis w as the lack of output from a significant portion of the programs. The best performer was MutPred, which had a weighted accuracy of 82.6% in the full datas...
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: Method Source Type: research

Related Links:

Sarepta Therapeutics Inc said on Monday the U.S. Food and Drug Administration declined to approve its newest treatment for Duchenne muscular dystrophy (DMD), citing safety concerns including the risk of infection and kidney toxicity.
Source: Reuters: Health - Category: Consumer Health News Tags: healthNews Source Type: news
The FDA has denied Sarepta Therapeutics ’ application for its second Duchenne muscular dystrophy treatment, despite the company producing twice the amount of data behind its controversial first product approval in 2016. Sarepta (Nasdaq: SRPT) had hoped to launch a treatment called golodirsen that would have doubled its reach among youn g boys with the disease. The drug, like Sarepta’s sole commercial treatment, was developed to skip over the faulty gene that prevents young boys with the disease…
Source: bizjournals.com Health Care:Pharmaceuticals headlines - Category: Pharmaceuticals Authors: Source Type: news
The U.S. Food and Drug Administration declined to approve Sarepta Therapeutics Inc's newest treatment for Duchenne muscular dystrophy (DMD), a rare muscle-wasting disorder that mainly affects boys, the company said on Monday.
Source: Reuters: Health - Category: Consumer Health News Tags: healthNews Source Type: news
This report presents a novel technique termed the pharyngeal clearance maneuver, which uses a modified application of the mechanical insufflation-exsufflation device to mobilize “secretion burden” at the portion of the trachea above the tracheostomy cuff during cuff deflation. Utilization of this strategy may reduce the risk of aspiration, infection, and respiratory compromise for patients with high cervical spinal cord injury in the acute rehabilitation setting. It is of particular benefit for those whose cuffs are being deflated for the first time and who may have large secretion volumes above the cuff. It ca...
Source: American Journal of Physical Medicine and Rehabilitation - Category: Rehabilitation Tags: Brief Reports Source Type: research
Authors: Muntoni F, Desguerre I, Guglieri M, Osorio AN, Kirschner J, Tulinius M, Buccella F, Elfring G, Werner C, Schilling T, Trifillis P, Zhang O, Delage A, Santos CL, Mercuri E Abstract Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (DMD) in clinical practice (NCT02369731). Here, we describe the initial demographic characteristics of the registry population. Patients &methods: Patients will be followed up from en...
Source: Journal of Comparative Effectiveness Research - Category: General Medicine Tags: J Comp Eff Res Source Type: research
Limb-girdle muscular dystrophies (LGMDs) belong to few neuromuscular disorders mainly involving pelvic and shoulder girdle muscles. Also, cardiac or pulmonary complications, increased rhabdomyolysis risk when ...
Source: BMC Anesthesiology - Category: Anesthesiology Authors: Tags: Case report Source Type: research
Source: Clinical Nutrition - Category: Nutrition Authors: Tags: Paediatrics II Source Type: research
Duchenne Muscular Dystrophy (DMD) is the most common muscle disease in children, and there are no effective therapies for DMD or Becker Muscular Dystrophy (BMD). Currently, targeted gene therapy treatments hav...
Source: BMC Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Research article Source Type: research
Duchenne muscular dystrophy (DMD) is a genetic disease evoked by a mutation in the dystrophin gene. It is associated with progressive muscle degeneration and increased inflammation. Up to this date, mainly ant...
Source: Skeletal Muscle - Category: Research Authors: Tags: Research Source Type: research
Conditions:   Limb-girdle Muscular Dystrophy;   Becker Muscular Dystrophy Intervention:   Drug: Prednisone Sponsor:   Northwestern University Enrolling by invitation
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
More News: Genetics | Muscular Dystrophy | Reflex Sympathetic Dystrophy | Statistics | Study