[CIS PIDD] [cis-pidd] Puzzling X-linked SCID case

[CIS-PIDD]

Thanks Mike and Gigi! I will look into checking his CD132 expression and sequencing the entire gene on his T cells. 

Angie

> On Jan 21, 2017, at 4:36 PM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org> wrote:
> 
> Absolutely correct! There may be a second site mutation that introduces an in frame splice site
> 
> Gigi Notarangelo
> 
> Sent from my iPhone
> 
> On Jan 21, 2017, at 4:59 PM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org> wrote:
> 
>> Hi Angie,
>> 
>> I agree with your first thought about somatic reversion.  If your test was only looking for a switch back to wt sequence at the original mutation site, you could be missing a dowstream second mutation that might allow re-initiation.  I would suggest sequencing the full gene.  I'm wondering if you may need to do sorted sequencing to see enough of a signal.    Another possibility would be to look at transcripts of cd132, as I'm betting you will see a slightly shortened transcript in revertant cells.
>> 
>> Best
>> Mike
>> 
>> On Jan 21, 2017, at 12:05 PM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org> wrote:
>> 
>>> Hi all 
>>> 
>>> I have an interesting post transplant X-linked SCID case and I’d like to see if others have thoughts about what is going on or have had similar cases. 
>>> 
>>> The patient is a now 2 year old male with X-linked SCID (c.269+1G>A mutation). He was diagnosed based on NBS and family history. He had a matched sibling (2 year old healthy sister, not a carrier) who served as his bone marrow donor for his unconditioned transplant on 1/8/15. He had no transplant related complications and no infections. By day +28 after transplant he had >500 CD3 T cells, all of which were donor in origin. By 6 months post transplant, he was off immune globulin replacement, had normal lymphocyte numbers, proliferation, TRECs and RTE. T cells remained 100% donor. 
>>> 
>>> At 1.5 years post transplant T cell donor chimerism had dropped to 20%. However, he continued to have normal lymphocyte numbers and B/T cell function. Now at 2 years out, his T cell chimerism is 9% donor. Lymphocyte numbers, immune globulin levels, proliferation, TREC, RTE all remain normal. Clinically doing fantastic — growing, developing normally, no infections. 
>>> 
>>> Somatic reversion was considered and our molecular diagnostics lab designed a real time quantitative PCR specific for his mutation to investigate this. They did not find any evidence of somatic reversion. 
>>> 
>>> He has never had myeloid donor chimerism. B cell donor chimerism has ranged from 5-10% and is stable. NK cell donor chimerism has ranged from 75-85% and is stable. 
>>> 
>>> I’m stumped. Thanks in advance for any thoughts on why we are seeing a significant drop in T cell chimerism, but normal immune reconstitution. 
>>> 
>>> Angie
>>> 
>>> ----
>>> Angela Smith, MD, MS
>>> Assistant Professor
>>> Pediatric Blood and Marrow Transplant
>>> University of Minnesota
>>> 420 Delaware Street SE
>>> MMC 484
>>> Minneapolis, MN 55455
>>> Phone 612 625 7253
>>> Fax 612 626 2815
>>> 
>>> 
>>> <PastedGraphic-1.tiff>
>>> 
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