[CIS PIDD] [cis-pidd] DOCK8 mutation

[CIS-PIDD]

Dear Chris,

indeed a lot of DOCK8 mutations are large deletions. You could test DOCK8 protein expression by flow cytometry and analyze T cells more profoundly (i.e. CD45RA and CCR7) to see if there is loss of naivety.

Best, Fabian


Fabian Hauck, MD, PhD
Head of Immunodeficiency Unit and Immunological Diagnostics Laboratory
Consultant Hematologist/Oncologist
Dr. von Hauner Children's Hospital
Klinikum der Universität München
Campus Innenstadt
Lindwurmstrasse 4, 80337 Munich
Phone: +49 (89) 4400-53931
Fax: +49 (89) 4400-53964
Email: fabian.hauck at med.uni-muenchen.de

The Klinikum der Universität München is an Institution under Public Law



-----Ursprüngliche Nachricht-----
Von: CIS-PIDD [mailto:cis-pidd at lists.clinimmsoc.org] 
Gesendet: Donnerstag, 30. Juni 2016 00:09
An: CIS-PIDD
Betreff: Re: [cis-pidd] DOCK8 mutation

You might talk with Talal Chatila. He has a patient with a point mutation causing Dock8 but most have large deletions (per him). 0.37% freq is pretty high...even if you had missed a deletion on the other allele

James



Sent from my iPhone

On Jun 29, 2016, at 4:36 PM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>> wrote:

I wasn't clear.

The variant is heterozygous.  So I was wondering if dominant negative should be considered?

Chris



From: "cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>" <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: Wednesday, June 29, 2016 at 3:08 PM
To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Subject: Re: [cis-pidd] DOCK8 mutation

Is the variant homozygous?



Prof Stuart Tangye | Head, Immunology Division Head, Immunology & Immunodeficiency Lab Garvan Institute of Medical Research
384 Victoria Street, Darlinghurst, NSW 2010<x-apple-data-detectors://1>

NHMRC Principal Research Fellow

Professor, St Vincent's Clinical School, Faculty of Medicine, UNSW Australia


T: + 61 (0)2 9295 8455<tel:+%2061%202%209295%208455> I M: + 61 (0) 413 390 306<tel:+%2061%20413%20390%20306>  I F: +61 (0)2 9295 8404<tel:+61%202%209295%208404>  I E: s.tangye at garvan.org.au<mailto:s.tangye at garvan.org.au>

www.garvan.org.au/resear<http://www.garvan.org.au/research/immunology/immunobiology-and-immunodeficiency>ch/<http://www.garvan.org.au/research/immunology/immunobiology-and-immunodeficiency>immunology/immunobiology-and-immunodeficiency<http://www.garvan.org.au/research/immunology/immunobiology-and-immunodeficiency>

On 30 Jun 2016, at 05:45, CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>> wrote:

Hi,

I was asked to see a 23m/o with severe AD and milk allergy after his local allergist sent HIES gene panel to GeneDX.  His DOCK8 sequence came back as follows: "Y1272C variant in the DOCK8 gene, which is of unknown significance."  Exon level array confirmed no duplications or deletions in DOCK8.  This variant has not been reported as benign, but per report noted to be present at a frequency of 0.36% in the 1000 genomes project. This amino acid change is predicted to change protein secondary structure.

The local allergist did some immune testing which demonstrated normal for age T and B cell numbers, normal immunoglobulin levels, protective tetanus antibody titer, and normal T cell proliferation to mitogens and tetanus toxoid.

Clinically, the child has been thriving.  He has had a few localized staph infections that responded to topical antibiotics.  He safely tolerated live vaccines. And his AD has improved with better skin care.


My suspicion is this is a benign variant.  I suggested the parents undergo genetic testing for targeted area.

Any other thoughts?

Thank you

Chris


Christine M. Seroogy MD,  FAAAAI
Associate Professor
University of Wisconsin School of Medicine and Public Health Department of Pediatrics Division of Allergy, Immunology & Rheumatology
1111 Highland Avenue
4139 WIMR
Madison, WI  53705-2275
phone: 608-263-2652
fax: 608-265-0164







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