Around 13% of MS cases are of genetic origin. 12 pathogenic variants.

A forum to discuss research on the origins of MS and its development.
Post Reply
User avatar
frodo
Family Elder
Posts: 1355
Joined: Wed Dec 02, 2009 3:00 pm
Contact:

Around 13% of MS cases are of genetic origin. 12 pathogenic variants.

Post by frodo » Tue Aug 13, 2019 7:38 am

https://www.ms-uk.org/scientists-edge-c ... -sclerosis

Of people diagnosed with MS, only 13% are believed to have a genetic form of the disease, but those presenting the mutations identified in this new study were estimated to have an up to 85% chance of developing MS in their lifetime.

Original source

https://journals.plos.org/plosgenetics/ ... en.1008180

Discussion

The existence of Mendelian forms of MS has been a recurrent topic of controversy, despite the evidence for familial aggregation, and the measurable increased disease risk for blood-relatives of MS patients [7, 143]. In this study we present the genetic characterization of 34 multi-incident MS families, which have nominated pathogenic variants in 12 genes.

A monogenic cause for MS could not be identified for 22 families. This was not an unexpected outcome given that complex diseases frequently are genetically heterogeneous, even within families In these families, pathogenic variants might have been overlooked given that WES technologies are not only unable to assess variants in non-coding regulatory regions, but also do not efficiently capture and sequence all coding exons, and are largely unsuited for the identification of copy number variations and rearrangements which may be responsible for the onset of disease

The genes harboring rare disease-causing variants for familial MS, herein or previously described, play critical roles in cellular cation homeostasis, and the regulation of transcription and activation of inflammatory mediators; suggesting a disruption of the innate immune system as the common underlying biological mechanism for the initiation of MS symptoms [,,,]

Although replication of our findings in additional multi-incident MS families is necessary to confirm a pathogenic role for these genes and rare variants, they suggest disruption of innate immunity, inflammation, angiogenesis and cation homeostasis as critical processes in the onset of Mendelian forms of MS. Although these genes provide a mechanistic insight into the etiology of disease, it should be noted that not all family members harboring the nominated disease-causing variants developed MS (Fig 2). Therefore, despite the highly susceptible genetic background created by these variants, additional genetic, epigenetic or environmental factors are likely required to trigger the onset of MS.

Although the variants identified in these families are rare, they provide the means for the development of cellular and animal models based on human genetic etiology. Models in which to further characterize the biological pathways disrupted in MS patients, and develop and assess the efficacy of novel therapeutic options tackling the pathophysiological processes of MS.

In addition, we envision gene screening being used as a tool for disease confirmation, and accurate risk assessment in healthy family members of MS patients. Following the confirmation of pathogenicity in additional MS families, and with the knowledge gained from characterizing newly developed models of MS based on the identified variants, we foresee the development of personalized treatments for MS patients, and preventative strategies for at risk individuals.

In conclusion, the implementation of WES in multi-incident MS families have nominated pathogenic variants in 12 genes, which highlight innate immunity and inflammatory response as critical processes leading to the onset of MS. A global effort towards the analysis of additional MS families, and the characterization of the biological processes disrupted by these variants, is necessary to expand our knowledge and understanding of the molecular and biological mechanisms underlying the genesis of MS. This gained knowledge is essential to drive the development of personalized medicine approaches with the potential to improve treatment efficacy and patient prognosis.

User avatar
frodo
Family Elder
Posts: 1355
Joined: Wed Dec 02, 2009 3:00 pm
Contact:

New paper about the same

Post by frodo » Fri Aug 16, 2019 10:15 am

HLA-DRB1 differences in allelic distribution between familial and sporadic multiple sclerosis in a Hellenic cohort

https://www.tandfonline.com/doi/abs/10. ... 19.1655382

Conclusion: We propose possible HLA-DRB1 allelic distribution differences between fMS and sMS, which become more apparent as proximity of affected relative/-es in fMS increases, supporting a rather degraded role of DRB1 alleles in fMS HLA/immunogenetics and indicating the concomitant implication of other HLA and non-HLA polymorphisms.

Post Reply
  • Similar Topics
    Replies
    Views
    Last post