Karin R. Engelhardt, PhD, Michael E

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Presentation transcript:

The extended clinical phenotype of 64 patients with dedicator of cytokinesis 8 deficiency Karin R. Engelhardt, PhD, Michael E. Gertz, PhD, Sevgi Keles, MD, Alejandro A. Schäffer, PhD, Elena C. Sigmund, BSc, Cristina Glocker, PhD, Shiva Saghafi, MSc, Zahra Pourpak, MD, PhD, Ruben Ceja, MSc, Atfa Sassi, PhD, Laura E. Graham, BSc, MBChB, Michel J. Massaad, PhD, Fethi Mellouli, MD, Imen Ben-Mustapha, MD, Monia Khemiri, MD, Sara Sebnem Kilic, MD, Amos Etzioni, MD, Alexandra F. Freeman, MD, Jens Thiel, MD, Ilka Schulze, MD, Waleed Al-Herz, MD, Ayse Metin, MD, PhD, Özden Sanal, MD, Ilhan Tezcan, MD, Mehdi Yeganeh, MD, Tim Niehues, MD, Gregor Dueckers, MD, Sebastian Weinspach, MD, Turkan Patiroglu, MD, Ekrem Unal, MD, Majed Dasouki, MD, Mustafa Yilmaz, MD, Ferah Genel, MD, Caner Aytekin, MD, Necil Kutukculer, MD, Ayper Somer, MD, Mehmet Kilic, MD, Ismail Reisli, MD, Yildiz Camcioglu, MD, Andrew R. Gennery, MD, Andrew J. Cant, MD, Alison Jones, MD, Bobby H. Gaspar, MD, Peter D. Arkwright, MD, DPhil, Maria C. Pietrogrande, MD, Zeina Baz, MD, Salem Al-Tamemi, MD, Vassilios Lougaris, MD, Gerard Lefranc, PhD, Andre Megarbane, MD, PhD, Jeannette Boutros, MD, Nermeen Galal, MD, Mohamed Bejaoui, MD, Mohamed- Ridha Barbouche, MD, PhD, Raif S. Geha, MD, Talal A. Chatila, MD, MSc, Bodo Grimbacher, MD Journal of Allergy and Clinical Immunology Volume 136, Issue 2, Pages 402-412 (August 2015) DOI: 10.1016/j.jaci.2014.12.1945 Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Schematic representation showing DOCK8 mutations in 44 of 46 families. Mutations in 2 families (1 with a retained intronic sequence and 1 without DOCK8-specific mRNA expression despite wild-type exonic sequences) are not shown. Straight lines depict multiexon deletions with undetermined breakpoints (gray, heterozygous). With the exception of the compound heterozygous multiexon deletion, all mutations were homozygous. DHR, DOCK homology region. Journal of Allergy and Clinical Immunology 2015 136, 402-412DOI: (10.1016/j.jaci.2014.12.1945) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Characteristics of DOCK8-deficient patients. A, Age at evaluation is represented by black dots, and age at death is represented by black crosses. B, Kaplan-Meier survival curve, with the 95% CI indicated by dotted lines. C, NIH HIES score. All 57 patients with information about HIES scores were included. Journal of Allergy and Clinical Immunology 2015 136, 402-412DOI: (10.1016/j.jaci.2014.12.1945) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Eosinophil and lymphocyte counts and serum immunoglobulin levels in DOCK8-deficient patients. A, Counts of several lymphocyte subtypes in blood. Gray areas represent age-adjusted normal ranges.11 B, IgE levels and eosinophil counts (normal, 100-500 cells/μL12; highly increased, >800 cells/μL10). Heavy dotted black line, 800 cells/μL. C, Patients' IgM, IgA, and IgG levels. Gray areas represent published normal ranges.13 Triangles depict high values, circles depict normal values, and crosses depict low values, according to the laboratories' own normal ranges. Journal of Allergy and Clinical Immunology 2015 136, 402-412DOI: (10.1016/j.jaci.2014.12.1945) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Journal of Allergy and Clinical Immunology 2015 136, 402-412DOI: (10.1016/j.jaci.2014.12.1945) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Journal of Allergy and Clinical Immunology 2015 136, 402-412DOI: (10.1016/j.jaci.2014.12.1945) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Journal of Allergy and Clinical Immunology 2015 136, 402-412DOI: (10.1016/j.jaci.2014.12.1945) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions