[CIS PIDD] [cis-pidd] STXBP2

Thu Jun 8 20:52:02 EDT 2017

Hi Tony,

I have a patient with a heterozygous R65Q mutation in STXBP2. She has absent NK function and abnormal CD107a. She is an 8yF with what I would describe as an ALPS-like disease with a smoldering fever, cytopenias and splenomegaly, but no fulminant HLH.

We are thus far treating her much like ALPs, initially with steroid (prednisone), to which she responded, and now with cellcept, which she is responding to thus far as well.

This mutation is published as a DOMINANT NEGATIVE mutation by Sesspott WA et al Blood 2015. The penetrance, however, is incomplete.

Of note, we are trying to get targeted analysis on mom and dad. Mom had some strange lymphadenopathy in her 20s, but nothing like her daughter.

Hope this is helpful,
Chris

Christian Wysocki MD, PhD
Assistant Professor
UT Southwestern Medical Center
Division of Allergy and Immunology
5323 Harry Hines Boulevard, F4.100B
Dallas, TX 75390-8859
Ph: 214-648-8909
Fax: 214-648-9102

From: cis-pidd at lyris.dundee.net [mailto:cis-pidd at lyris.dundee.net] On Behalf Of CIS-PIDD
Sent: Thursday, June 08, 2017 4:09 PM
To: CIS-PIDD
Subject: Re: [cis-pidd] STXBP2

If STXBP2 is the culprit, CD107A degranulation should be abnormal.

Ashish
Ashish Kumar, MD, PhD
Associate Professor
Director, Pediatric Hematology-oncology fellowship program
Director, Langerhans cell histiocytosis center
Cincinnati Children's Hospital Medical Center

On Jun 8, 2017, at 4:53 PM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>> wrote:
Hi Tony,

It has been reported at least once:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351505/<https://urldefense.proofpoint.com/v2/url?u=https-3A__www.ncbi.nlm.nih.gov_pmc_articles_PMC4351505_&d=DwMF-g&c=P0c35rBvlN7D8BNx7kSJTg&r=7_Xi_iO9LJTHr-vy99jYOfSlhgVB29ez3xj6iG4Kpn0&m=lkwzVTflYXt2TkmT_tlN3_TSOr-9lUeZ_ZArrwBcDJo&s=ch-5_I0NfNJ1-MciIDTS-nCtLdWHZhmno6BLlaH9SMA&e=>

 - Ivan

From: <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>> on behalf of CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
Reply-To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Date: Thursday, June 8, 2017 at 3:47 PM
To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Subject: [cis-pidd] STXBP2

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I have a 20 year old female patient who has a lifelong history of recurrent febrile illnesses, mainly viral. Many without prominent symptoms other than fever, often with oral aphthous ulcers, maybe one or two occurrences of vaginal ulcers. Colleagues in rheumatology have been treating her as an autoinflammatory disorder, she responded partially to colchicine, but broke through frequently with lots of oral ulcers. She also happens to have multiple personality disorder.

The only immunologic abnormality is absent or very low NK function on 2 occasions.

A recent NGS panel showed a few heterozygous changes including deletion of most of one copy of TTC37, and point mutations in C3, RAG1, and STXBP2. I find the latter most curious of the lot, and I am confirming the result by Sanger sequencing.

Does anyone know of HLH associated with heterozygous mutation in STXBP2?
Thank you.
Tony B.

Francisco A. Bonilla, M.D., Ph.D.
Director, Clinical Immunology Program, Boston Children's Hospital
Associate Professor of Pediatrics, Harvard Medical School

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