Additional Diverse Findings Expand the Clinical Presentation of DOCK8 Deficiency
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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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- Additional Diverse Findings Expand the Clinical Presentation of DOCK8 Deficiency
Journal of Clinical Immunology
Volume 32, Issue 4 , pp 698-708
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- combined immunodeficiency
- epidermodysplasia verruciformis
- sclerosing cholangitis
- CNS lymphoma
- Industry Sectors
- Author Affiliations
- 1. Department of Pediatric Immunology, Hacettepe University Faculty of Medicine, Ankara, 06100, Turkey
- 2. Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10CRC, Room 5-3940, 10CRC Center Drive, MSC 1456, Bethesda, MD, 20892, USA
- 3. Department of Dermatology, Hacettepe University Faculty of Medicine, Ankara, 06100, Turkey
- 4. Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
- 5. Department of Pediatric Neurology, Hacettepe University Faculty of Medicine, Ankara, 06100, Turkey
- 6. Department of Pediatric Gastroenterology, Hacettepe University Faculty of Medicine, Ankara, 06100, Turkey
- 7. Department of Pediatric Oncology, Hacettepe University Faculty of Medicine, Ankara, 06100, Turkey
- 8. Department of Pathology, Hacettepe University Faculty of Medicine, Ankara, 06100, Turkey
- 9. Department of Radiology, Hacettepe University Faculty of Medicine, Ankara, 06100, Turkey