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View Full Version : Familial Mediterranean fever in descendants Puritans of Southold, Long Island



Jean M
01-23-2014, 06:57 PM
Amazing story from Dr Janine Jagger - All I Want for Ramadan Is My Own Mutation

http://www.huffingtonpost.com/janine-jagger/all-i-want-for-ramadan-is_b_4214527.html

Timothy
01-24-2014, 05:14 AM
Wow! My Mom and her sister both share 1 mutation (not both) in A744S, 1 of the 10 that 23andMe tests for in the MEFV gene. Their known ancestry on every line researched is Colonial American, mostly English/Irish, including 1650's Boston, Mass. area. I couldn't understand how they got it with no known ancestry except Northern European. This explains a lot! They have had many odd maladies, esp. their deceased sister, who was virtually bedridden for years with various health issues. Thank You!

Jean M
01-24-2014, 07:30 AM
I notice that 23andMe does make the point that anyone could be a carrier.


Familial Mediterranean fever (FMF) is an auto-inflammatory disorder characterized by "attacks" that can include fever, chest and abdominal pain, swollen joints and rash. Long-term complications of the disease include infertility, arthritis and serious kidney damage. FMF is caused by mutations in the MEFV gene, which encodes pyrin, a protein involved in regulating the inflammatory responses of immune cells. FMF is inherited in a recessive manner, meaning that only a child who receives two mutated copies of the MEFV gene (one from each parent) will get the disease. The severity of disease depends on the particular mutations a person inherits. Although anyone can be a carrier for a mutation that causes FMF, these mutations are most commonly found in people with Turkish, Arab, Sephardic Jewish and Armenian ancestry.

alan
01-24-2014, 08:46 AM
That was a very interesting read.

Ann Turner
01-24-2014, 12:10 PM
I notice that 23andMe does make the point that anyone could be a carrier.
Right. There could be any number of founder mutations in different times and places. I would bet that the M in FMF has led to underdiagnosis in cases where there's no Mediterranean background to raise the index of suspicion.

Palisto
01-24-2014, 10:34 PM
Some data about FMF:
From here:
www.ncbi.nlm.nih.gov/pubmed/11464238
Five founder mutations, V726A, M694V, M694I, M680I and E148Q account for 74% of FMF chromosomes from typical cases (Armenians, Arabs, Jews, and Turks).


To give you an idea how frequent FMF mutations are in the Middle East and elsewhere (Carrier frequency, see below):
Armenians: 37%
Iraqi Jews: 30%
Non-Ashkenazi Jews: 24.4%
Ashkenazi Jews: 22.9%
Turks: 16.4%
Arabs: 15.1%
British: 2%

A very good summary can be found here:
http://omim.org/entry/249100

I collected MEFV SNP data of FMF carriers.
Interestingly, there is no variation in V726A. All V726A carriers belong to one MEFV haplotype suggesting a more recent origin.
https://docs.google.com/spreadsheet/ccc?key=0AgVZU9mN1R6ldEtEMTBsNzczbEJqT2lyd0FHXzhFZ Gc&usp=sharing

DMXX
01-25-2014, 03:06 AM
To give you an idea how frequent FMF mutations are in the Middle East and elsewhere (Carrier frequency, see below):


Any data on Kurds or Iranians? I have no family history of FMF and do not carry any of the mutations for it. Given the significant presence in Armenians, Turks and various Jewish populations, I'd deduce the Assyrians also have a fairly high carriage rate also.

Humanist
01-25-2014, 10:36 AM
I'd deduce the Assyrians also have a fairly high carriage rate also.

My grandmother is a carrier. Something she has in common, apparently, with some of her fellow Long Islanders! :)

Palisto
01-25-2014, 10:58 AM
Any data on Kurds or Iranians? I have no family history of FMF and do not carry any of the mutations for it. Given the significant presence in Armenians, Turks and various Jewish populations, I'd deduce the Assyrians also have a fairly high carriage rate also.

I am carrier for the V726A mutation.

Based on Bidari et al., 2010 (http://www.ncbi.nlm.nih.gov/pubmed/20549290) "the most frequent mutation [in 36 Iranian FMF patients] was M680I, followed by M694V, and V726A."

In Bonyadi et al., 2009 (http://www.ncbi.nlm.nih.gov/pubmed/19863562), 524 patients were tested for 15 known mutations in the MEFV gene. Of the alleles investigated, the most common mutation was p.M694V (42.4%), followed by p.V726A (17%), p.E148Q (16.2%), and p.M680I (c.2040G>C) (15.2%). The p.R761H mutation (4.7%) was found to be the most frequent among the rare mutations. The mutations p.M680I (c.2040G>A), p.I692del, p.M694del and p.K695R were not found in this cohort.



My grandmother is a carrier. Something she has in common, apparently, with some of her fellow Long Islanders! :)

I thought you are also a FMF carrier.

Hanna
01-27-2014, 06:06 PM
My maternal cousin has familial mediterranean fever. My aunt and I don't carry any of its mutations but my grandfather does (M694V CT). My cousin who has FMF was not DNA tested but obviously her father ( my uncle) got the mutation from my grandfather. My cousins mother must have also carried the mutation for my cousin to actually have the disease.

Janine
04-08-2015, 07:40 PM
Timothy, I just joined this group to respond to your post. I just tried to send you a message but I am not sure I succeeded. I am the author of the "All I want for Ramadan . ." story and I would like to follow up with you on your ancestry and see if another piece can be added to this FMF cohort of English colonists - that discovery was a total shock to me - I had no idea that my ancestry was loaded with Puritans and that the Puritans were loaded with a Middle Eastern disease. But after doing this research I was sure that there had to be others like me in this improbable cohort. Also, I would like to verify that your affected family has gotten appropriate treatment. I hope you get this message - please respond to my e-mail address: [email protected] I look forward to hearing from you.
Janine Jagger

Ignis90
04-09-2015, 09:09 AM
The "Arab" category is very broad, it should be more precise.


In addition to the aforementioned populations, FMF is also found (to a much lesser extent) in Berbers, Italians, Greeks and Iberians.




Prévalence et distribution des mutations de MEFV chez des Arabes originaires du Maghreb souffrant de fièvre familiale méditerranéenne, 2006

Abstract

Familial Mediterranean fever (FMF) is an autosomal recessive inherited disease caused by mutations in MEFV . This disease is characterized by recurrent episodes of fever accompanied with topical signs of inflammation. Some patients can develop renal amyloidosis. We prospectively investigated MEFV mutations in a cohort of 209 unrelated Arab patients from Maghreb (85 Algerians, 87 Moroccans, and 37 Tunisians) with a clinical suspicion of FMF. FMF is the main cause of periodic fever syndrome in Maghreb. The most frequent MEFV mutations in this cohort were M694V and M694I. These mutations account for different proportions of the MEFV mutations in Algeria (5%, 80%), Morocco (49%, 37%), and Tunisia (50%, 25%) patients. M694I mutation is specific to the Arab population from Maghreb. Other rare mutations were observed: M680L, M680I, A744S, V726A, and E148Q. We estimated the frequency of MEFV mutation carriers among the Arab Maghrebian population at around 1%, which is significantly lower than in non-Ashkenazi Jews, Armenians or Turks. To cite this article: L. Belmahi et al., C. R. Biologies 329 (2006).

"Arab" are Berbers in this context.

Arame
11-15-2015, 09:26 AM
There is a theory that some of this mutations are a back mutations to more archaic state. The reason is unknown but most probably it gave a selective advantage related to immune system response to germs. Otherwise it wouldn't become so prominent.
This pyrin protein is part of the innate immune system (https://en.wikipedia.org/wiki/Innate_immune_system) that controls the speed of mobilisation of leukocytes. This innate system is not specialised it is a generic defence system so it can be useful when a population is confronted to a unknown bacterial threat.
I have relatives who have this disease. Most probably I am also a carrier of M694V mutation.

Btw I wonder if I order an autosomal test from FTDNA will I get an answer about this mutation?