Autoinflammatory Alliance Board Member Dorelia Rivera Met with Top U.S. Health Officials

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Meeting with Kathleen Sebelius

Autoinflammatory Alliance board member Dorelia Rivera (in black shirt) meets with top U.S. health officials.

In August 2013, Autoinflammatory Alliance board member Dorelia Rivera met with the U.S. Secretary of Health and Human Services Kathleen Sebelius, Dr. Francis Collins the Director of the National Institutes of Health (NIH), Ms Kathy Russell the CEO of the Children’s Inn at the NIH, and Dr. Raphaela Goldbach-Mansky, who is an expert on autoinflammatory diseases and U.S. Federal Liaison to The Autoinflammatory Alliance.

Dorelia met with them, along with her family while she was at the Children’s Inn (pictured) at the National Institutes of Health (NIH) to increase awareness about the challenges and experiences of patients with autoinflammatory diseases.  It was a very helpful awareness meeting, and we are thankful that Dori could get the word out to the top official in the U.S. overseeing health care!  Thanks again Dori for all that you do.

Autoinflammatory Alliance’s Rare Disease Day 2014 Activities

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How the Autoinflammatory Alliance (formally the NOMID Alliance) was  Involved in Rare Disease Day 2014:

Rare Disease Legislative Associates (RDLA) had a number of events, including the RDLA Legislative Conference and Lobby Days in Washington DC.  Two of our NOMID Alliance board members and advocates, Carla Herbert and Julie Cunningham, represented patients with autoinflammatory diseases and our organization at the RDLA events for Rare Disease Day 2014. They met and worked with many other rare disease organizations and voiced the needs of our patients to legislators and policy makers in the U.S. government.  We prepared a one-page letter to share our message to the elected officials.

autoinflammatory alliance rare disease 2014

Autoinflammatory Alliance board member Julie Cunningham (3rd from left) co-chaired the Global Genes World Rare Disease Day effort.

In addition, Julie Cunningham was the co-chair for the Global Genes World Rare Disease Day effort and she did a great job. In addition to that, and the RDLA events in Washington DC, she also held a rare disease awareness event at Alverno High School in Pasadena, CA. They did a fantastic job telling the students all about the “Wear that You Care” campaign and handing out denim ribbons.  Julie and her family also filmed with her daughters a news story on rare diseases for Fox 5 News in San Diego. That story aired on Rare Disease Day and featured their experience with CAPS. Also featured in the news story was Dr. Hoffman, who is on The Autoinflammatory Alliance Medical Advisory Committee.

Carla Herbert was also involved in planning the New Jersey State House Event held on Monday, March 3rd, followed by a luncheon. Peter, Carla’s son spoke about living with a rare disease. Thank you Carla and Peter for your awareness efforts!

Colleen Paduani, board member and advocate, along with a speaker from NORD presented at a special Rare Disease Day Lunch & Learn event hosted by Rabobank in New York City at their headquarters. Rabobank also made a very generous donation to both organizations that day! Thank you for the donation, Rabobank, and to International Desk Manager Andre Hessels and IT’s Michel Angevare for organizing this awareness campaign within RI-NAW. Employees who chose to make a donation, and attend the Lunch n’ Learn received a boxed lunch, bracelet, and pin, and heard two guest speakers with rare diseases in their families explain how their lives have changed with this campaign’s support.

The Autoinflammatory Alliance is a nonprofit organization dedicated to helping those with autoinflammatory diseases.

Donate now to help with awareness, education, and research for these rare diseases.

Short Summary of Recent Studies on Familial Mediterranean Fever (FMF) and Single Mutation

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Over the last decade, several studies identify significant subsets (20-30%) of FMF symptomatic patients who carry only 1 MEFV mutation.  These individuals have FMF symptoms that respond to colchicine.  These studies include an NIH study by Booty et al (2009 Arthritis & Rheumatism),  Marek-Yagel (2009 Arthritis & Rheumatism), a study of French patients by French by Kone-Paut et al (2009 Rheumatology),  a study of  Armenian patients by Moradian et al (2010 J of Human Genetics), and a study of Western European caucasians by Federici (2012 Annals of Rheumatology Disease).

There are a wide number of MEFV mutations linked with FMF.  Across all FMF patients, nearly around 80% of MEFV mutations are accounted for by E148Q, M680I, M694I, M694V, and V726A. The percentages for the particular mutation in single mutation cases differ by the population under study.  In a study of Turkish patients by Ozdemir (2011 Molecular Biology Reports), 43% displayed the M694V mutation, 20% the E148Q,  15% the M680I, and 11% the V726A (11.32%).   The studies also indicate that individuals with 1 MEFV mutation exhibit symptoms that are often less severe than individuals with 2 mutations.  Also, individuals with 1 mutation show higher levels of other inflammation markers than individuals with no mutation, including among “healthy” individuals with 1 mutation.

Studies are beginning to appear in the literature that attempt to identify the reasons that the typically recessive MEFV  mutation begins to behave as if dominant, thereby causing the clinical symptoms of FMF. A review of the efforts is provided by Touitou (2013 Journal of Medical Genetics).  One general theme is that the relationship of inheritance and disease expression is more complex than suggested by the simple classical model of genetics (Booty et al 2009).  Instead, the body of evidence is suggesting that the environmental and “epigenetic” sources (molecular changes other than the underlying DNA sequence) are important in triggering disease expression in patients with single mutations.  A statistical evaluation of FMF patients by Jeru et al (2013 PLOS) lends support to this idea, suggesting that while single FMF patients show higher disease expression than individuals with no mutations, very careful analysis shows that the single FMF mutation is not the “cause” of FMF symptoms by itself in the classical sense of inheritance.

The process of recessive genes causing disease as if dominant is not unique to FMF or fever syndromes.  There are ongoing studies of recessive to pseudodominant process in under study in a number of diseases.  A search of Google Scholar for autosomal recessive to pseudodominance returns a number of current studies.

References

  1. Aslan. Familial Mediterranean fever with a single MEFV mutation: can a deletion resulting in α-thalassemia be the cause?  Journal of Human Genetics, 2011: 56, 169-171.
  2. Booty, et al.  Familial Mediterranean fever with a single MEFV mutation: Where is the second hit? Arthritis & Rheumatism 2009: 60, 1851–1861.
  3. Federci et al. Clinical impact of MEFV mutations in children with periodic fever in a prevalent western European Caucasian population. Ann Rheum Dis 2012;71, 1961-1965.
  4.  Jeru et al. The Risk of Familial Mediterranean Fever in MEFV Heterozygotes: A Statistical Approach. PLOS
  5. Kone-Paut et al. The clinical spectrum of 94 patients carrying a single mutated MEFV allele. Rheumatology (Oxford) 2009: 4,: 840–842. 
  6. Lachmann et al.  Clinical and subclinical inflammation in patients with familial Mediterranean fever and in heterozygous carriers of MEFV mutations. Rheumatology (Oxford) 2006; 45, 746–50. 
  7. Marek-Yagel et al. Clinical disease among patients heterozygous for familial Mediterranean fever. Arthritis & Rheumatism 2009: 60,1862–1866.  
  8. Moradian et al.  Genotype-phenotype studies in a large cohort of Armenian patients with familial Mediterranean fever suggest clinical disease with heterozygous MEFV mutations. J Hum Genet 2010: 55, 389–393.
  9. Ozdemir et al. Prevalence of known mutations in the MEFV gene in a population screening with high rate of carriers. Molecular Biology Reports, 2011: 38, 3195-3200.
  10. Ozen. Changing concepts in familial Mediterranean fever: Is it possible to have an autosomal-recessive disease with only one mutation? Arthritis & Rheumatism 2009: 60, 1575–1577. 
  11. Touitou.  Inheritance of autoinflammatory diseases: shifting paradigms and nomenclature. Med Genet 2013;50, 349-359.
  12. Touitou. The spectrum of familial Mediterranean fever (FMF) mutations. Eur J Hum Genet 2001; 9, 473–83.