Abstract
We describe seven Turkish children with DOCK8 deficiency who have not been previously reported. Three patients presented with typical features of recurrent or severe cutaneous viral infections, atopic dermatitis, and recurrent respiratory or gastrointestinal tract infections. However, four patients presented with other features. Patient 1–1 featured sclerosing cholangitis and colitis; patient 2–1, granulomatous soft tissue lesion and central nervous system involvement, with primary central nervous system lymphoma found on follow-up; patient 3–1, a fatal metastatic leiomyosarcoma; and patient 4–2 showed no other symptoms initially besides atopic dermatitis. Similar to other previously reported Turkish patients, but in contrast to patients of non-Turkish ethnicity, the patients’ lymphopenia was primarily restricted to CD4+ T cells. Patients had homozygous mutations in DOCK8 that altered splicing, introduced premature terminations, destabilized protein, or involved large deletions within the gene. Genotyping of remaining family members showed that DOCK8 deficiency is a fully penetrant, autosomal recessive disease. In our patients, bone marrow transplantation resulted in rapid improvement followed by disappearance of viral skin lesions, including lesions resembling epidermodysplasia verruciformis, atopic dermatitis, and recurrent infections. Particularly for patients who feature unusual clinical manifestations, immunological testing, in conjunction with genetic testing, can prove invaluable in diagnosing DOCK8 deficiency and providing potentially curative treatment.
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Acknowledgements
We thank the physicians who referred their patients to us and the patients and their relatives who participated in this study. We also thank Baran Erman for isolating RNA and performing the RT-PCR reaction on PBMC from patient 1–1. This work was supported in part by the Intramural Research Program of the National Institutes of Health, the National Institute of Allergy and Infectious Diseases, through the Lymphocyte Molecular Genetics Unit (LMGU) program. Sequencing was performed by the Genomics Unit of the Rocky Mountain Laboratories Research Technologies Section of the National Institute of Allergy and Infectious Diseases.
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Sanal, O., Jing, H., Ozgur, T. et al. Additional Diverse Findings Expand the Clinical Presentation of DOCK8 Deficiency. J Clin Immunol 32, 698–708 (2012). https://doi.org/10.1007/s10875-012-9664-5
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DOI: https://doi.org/10.1007/s10875-012-9664-5