This is difficult to try to get into with some one who is not a biologist...ect ...because its hard to explain in laymens terms..hmmm how to do this without boring science bull crap
Lets start with the idea that before you know if a gene is mutated...you have to know what the normal gene looks like. Most scientist caution against the genetic Marfans diagnosis because this has really not been done.
There was no extensive work done on the fibrillin gene prior to the Marfan syndrom connection and then a bunch of hasty work was done on MARFAN patients and a very small set of controls...thus there are still some VERY important questions that remain to be answered
1. How prevelant are these point mutations in the general public ?
2. a c.2648G>, a transition in exon21 may be found in high prevelance in Marfan patients...BUT it may also be idetified in the normal public. Where is the data to show how prevelant this mutation is in normal individuals ????????? That wasnt done for some odd reason.
3. What do the fibrillin mutations really do ??? Are they responsible for the full phenotyope or just part of it. For example fibrillin mutations have been found in people who are simply tall or have isolated skeletal features
http://www.ncbi.nlm.nih.gov/pubmed/7738 ... t=Abstract4. People develop full Marfan syndrome without ANY identifiable fibrillin mutation...infact up to 60% of Marfan patients will test to have normal fibrillin genes.
In one major study of 94 Marfan patients (ghent criteria diagnosed) ony 66 of them were found to have fibrillin mutations on any exon.
http://www.ncbi.nlm.nih.gov/pubmed/1170 ... t=Abstract. So roughly 30 of them HAD NORMAL FIBRILLIN GENES BUT THEY STILL HAD MARFAN SYNDROME
LOOK HERE IS MY BELIEF ON THIS THING. I HAVE NO DOUBT THAT THE FIBRILLIN PROTEIN IS INVOLVED IN MARFAN SYNDROME AND THAT A MUTATION IN THIS GENE MAY BE CONSIDERED TO BE OF A HIGHER PREVELANCE THAN NORMAL.
BUT IT IS OBVIOUS TO ANYONE WHO LOOKS AT THE RESEARCH THAT THERE IS MUCH MUCH MORE GOING ON HERE THAN JUST THE FIBRILLIN GENE. THE FACT THAT PEOPLE MAY HAVE FULL BLOWN MARFAN SYNDROME WHILE HAVING NORMAL FIBRILLIN GENES AUTOMATICALLY AND DEFINATIVELY DISQUALIFIES THE FIBRILLIN GENE MUTATION AS THE SOLE CAUSE OF MARFAN SYNDDROM. DOWN THE ROAD MANY MORE MUTATIONS AS WELL AS POST TRANSLATIONAL MODIFICATION ERRORS AND ERRORS IN GENE ACTIVATION WILL BE IDENTIFIED AS THE REAL CAUSE OF MARFAN.
TRUST ME THE FIBRILLIN THING IS JUST THE TIP OF THE ICE BERG AS AN EXAMPLE....PEOPLE WITH MARFANS AND NO FIBRILLIN MUTATION MAY HAVE UP REGULATION OF THE MMP-9 GENE...WHIS WOULD LEAD TO ABNORMALLY FAST BREAKDOWN OF NORMAL FIBRILLIN AND HIGH TGFB AS A RESULT !!!! THAT WOULD LEAD TO THE SAME PHENOTYPE....THERE IS ALSO EVIDENCE THAT NORMAL FIBRILLIN MAY JUST NOT BE GETTING INTO THE EXTRACELLULAR MATRIX PROPERLY DUE TO A MUTATION IN ON OF A MILLION OTHER PROTEINS THAT ARE INVOLVED IN THAT PROCESS...END RESULT IS THE SAME PHENOTYPE.
WHAT COULD BE GOING ON WITH YOU AND YOR DAD IS THAT ANOTHER MUTATION OR UP REGULATION OF AN NORMAL GENE ECT...IS CAUSING THE DISEASE PROCESS OF AORTIC ANEURYSM...WHILE YOU JUST HAPPEN TO HAVE A MUTATION IN ONE OF THE EXONS OF THE FIBRILLIN GENE THAT ARE GIVING YOU ...NOT HIM THE SKELETAL MANIFESTAIONS. THAT PARTICULAR MUTATION MAY HAVE SKIPPED A GENERATION, BE SPONATNEOUS OR CONTRIBUTED BY THE MOTHER...WHO MAY HAVE NO SYMPTOMS WHAT SO EVER....ALL THE WHILE THE REAL CULPRIT REMAINS UNIDENTIFIED....
