[CIS PIDD] [cis-pidd] periodic fever patient

[CIS-PIDD]

Hello,
This mutation is known as a low-penetrance mutation or polymorphism. (It is a bit like the R92Q mutation in the TNFRSF1A gene for TRAPS, for those to whom that means anything). In this case the literature is very confusing, because this change is also known as c.2107C>A (p.Gln703Lys) = Q703K.
It is found in a prevalence in the general population of 5-11 %. It probably confers upon carriers some increased likelihood or an increased intensity of inflammatory response (as was a.o. shown in the article linked by the previous responder), but I would be careful of really calling it directly disease-causing, and careful of now considering your search for the cause of disease in this boy finished. It may predict that if you need more intense treatment and still have no diagnosis, IL-1 blockade would be something to try.

Some links:
A good resource to look up mutations of the hereditary autoinflammatory genes is: infevers - http://fmf.igh.cnrs.fr/ISSAID/infevers/index.php - they keep a database of all reported mutations. I encourage everyone to report findings as well.

A search for Q705K in Pubmed also helps: http://www.ncbi.nlm.nih.gov/pubmed/?term=Q705K
It is also known under the following number for a polymorphism: rs35829419 C>A - for example this link collects case control studies with this polymorphism, linking it with increased susceptibility to multiple diseases: http://www.ncbi.nlm.nih.gov/pubmed/26535712

Regards,
Anna



A. Simon, MD PhD
Internist, Infectious disease specialist
Associate Professor
Department of Internal Medicine
anna.simon at radboudumc.nl<mailto:anna.simon at radboudumc.nl>
T +31 (0)24 361 88 19

Radboud university medical center
P.O.Box 9101, 6500 HB Nijmegen (463), The Netherlands
Geert Grooteplein 8 (route 463)
www.radboudumc.nl<http://www.radboudumc.nl>
www.ncia.nl<http://www.ncia.nl>

Present: Monday - Friday




Van: CIS-PIDD [mailto:cis-pidd at lists.clinimmsoc.org]
Verzonden: maandag 21 december 2015 21:23
Aan: CIS-PIDD
Onderwerp: [cis-pidd] periodic fever patient

Hi all,

I just began seeing a 3yo Caucasian male with periodic fevers occurring since 6 months of age. Fevers originally occurred once every 3-4 weeks associated only with lethargy. He did have rash and conjunctivitis with 1 fever several months ago but these other symptoms never occurred again. No lymphadenitis, sore throat, arthritis, vision trouble, or anything else. He was treated with oral prednisone for presumed PFAPA which did abort the fevers after the first or second dose. The prednisone still works but the synchronicity of fevers has been thrown off, now occurring weekly to monthly and 1 interval of 6 weeks. Without prednisone, fevers reach 103-104F and last ~3days. He is growing well, has no family history or consanguinaity, and has normal baseline labs (CBC, CMP, urinalysis). CRP was elevated during 1 febrile episode in which labs were drawn (WBC elevated also, but otherwise normal). Neonatal period was uneventful. Over the last several months, he has developed chronic abdominal pain that is worse during febrile episodes but can occur independent of fever as well. He had an ultrasound of the abdomen that was normal but no other imaging. He was referred to our group after a periodic fever panel was performed and he was found to have a heterozygous mutation in exon 5 of NLRP3 c.2113C>A p.Gln705Lys that is predicted to be damaging.

I have looked in the literature and am having a hard time finding this mutation as previously described and since his manifestations are not really consistent with CAPS, I question what this mutation means. Does anyone have any insight as to whether this mutation is truly disease causing or has anyone seen this mutation in a patient with CAPS before?

Thanks,
Jen Leiding

Jennifer Leiding, MD
Assistant Professor
University of South Florida
Department of Pediatrics
Division of Allergy, Immunology, and Rheumatology
Children's Research Institute
140 - 7th Avenue South Box 9680
St. Petersburg, Florida 33701
Phone: 727.553.1304
Fax: 727.553.1295


---

You are currently subscribed to cis-pidd as: anna.simon at radboudumc.nl<mailto:anna.simon at radboudumc.nl>.

To unsubscribe click here: http://cts.dundee.net/u?id=96396401.638f180a71225b491ec21119cc184e95&n=T&l=cis-pidd&o=3371273

(It may be necessary to cut and paste the above URL if the line is broken)

or send a blank email to leave-3371273-96396401.638f180a71225b491ec21119cc184e95 at lyris.dundee.net<mailto:leave-3371273-96396401.638f180a71225b491ec21119cc184e95 at lyris.dundee.net>

Het Radboudumc staat geregistreerd bij de Kamer van Koophandel in het handelsregister onder nummer 41055629.
The Radboud university medical center is listed in the Commercial Register of the Chamber of Commerce under file number 41055629.

---
You are currently subscribed to cis-pidd as: pagid at list.clinimmsoc.org.
To unsubscribe click here: http://cts.dundee.net/u?id=96396833.5a9591ccd1e327fe6bc4d1543298c482&n=T&l=cis-pidd&o=3372211
or send a blank email to leave-3372211-96396833.5a9591ccd1e327fe6bc4d1543298c482 at lyris.dundee.net
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <https://pairlist7.pair.net/pipermail/pagid/attachments/20151222/3c42dfdb/attachment.html>