This Is MS Multiple Sclerosis Community: Knowledge & Support

The CNVs [copy number variations] contained in the HLA locus region in patients with the novel phenotype of CCSVI/VM and MS were mapped in detail, demonstrating a significant correlation between the number of known CNVs found in the HLA region and the number of CCSVI-VMs identified in patients. Pathway analysis revealed common routes of interaction of several of the genes involved in angiogenesis and immunity contained within this region. Despite the small sample size in this pilot study, it does suggest that the number of multiple polymorphic CNVs in the HLA locus deserves further study, owing to their possible involvement in susceptibility to this novel MS/VM plus phenotype, and perhaps even other types of the disease.

Did you tell cheerleader/alliance about it? sounds like one for the books.

Dr. Alessandra Ferlini- geneticist at Universite deglie Studi di Ferrara
SNPs are single nucleotide polymorphisms- and they reveal a multi-loci susceptibility to MS. The 4 specific loci are MS1, MS3, MS4, MS2. These are the chromosomes most linked to MS

Genetics is still questioned in this research, since there are undefined environmental factors.

Genome inflation- a characteristic of SNPs may hamper the true definition of identified genetic loci by SNP association. More studies are needed.

Interactome- the interaction of phonemics, genomics, preteomic, metabolic studies- all together-
This is done in genomic studies using CGH array rather than SNPs

The Ferrara study looked at CNVs (copy number variations) of chromosome 6p21.32 (HLA locus) in CCSVI patients.
CGH verified the occurrence of CNVs in the major locus of MS patients.
15 unrelated CCSVI patients were tested. No relation between the topography of CNVs and phenotype were shown....
but there was a significant relation between the number of extragenic CNVs and the phenotype correlated with venous malformations.

HSPAIL, HSPIA, HSPIB (heat shock proteins) were related to angiogeniesis and immunity. HLADLAZ and CD4 are involved in proinflammatory disease and tumor angiogensis. There are multiple gene disorders, and environment has a large influence.

The genome imbalance may be sensitive to environmental factors.

There was a significant correlation between the number of CNVs and the number of venous malformations. The number of polymorphic CNVs in the HLa region linked to MS does correlate with the number of venous malformations in MS patients.

This is a new way to study genetic disorders- to look for mutations on more than one genome. It is a very complex system, and cannot be narrowed to one genome.

Dr. Frohman asks if this has been tested in families? Are there genes affected in relatives with other autoimmune diseases?

Dr. Ferlini answers that this is a pilot study, and it is the first time looking at this paradigm. Future testing will look at families.

Dr. Lee comments that we have much genetic data on lymphatic malformation, yet no studies on the genetics of venous malformation. The veno-lymphatic systems need to be brought together. They have been separated and we need more venous information.

Dr. Ferlini comments that a similar phenotype can involve many genes, it depends on how they interact in the pathway. We need to locate many genes and understand how they interrelate, when they switch on and off, and how they interact in polygenetic disorders.

I'm sorry this is way over my head - (thanks CeCe for putting it in plain English).

Is this discovery the beginning of proof that MS & CCSVI are genetically inherited disorders? Or am I completely misunderstanding the significance?

I'd wondered if CCSVI birth defects were the cause of something that happens to the fetus in the womb, like say having a mother that smokes or has a nutritional deficiency or whatever else causes birth defects. But does this mean it's actually inherited thru ancestry?

And what does this imply for gene therapy (another topic I know zero about but am wondering).

Sorry for being thick & asking stupid questions - MS brain here.

L---it's been surreal seeing my writing show up on random blogs and websites, always uncredited, and in some cases other people putting their names on it. Whatever. As long as the info gets out there, I guess. I ain't getting paid anyway
cheer

L---it's been surreal seeing my writing show up on random blogs and websites, always uncredited, and in some cases other people putting their names on it. Whatever. As long as the info gets out there, I guess. I ain't getting paid anyway
cheer