Additional Diverse Findings Expand the Clinical Presentation of DOCK8 Deficiency

作者：S**** Ozden^*; Jing Huie; Ozgur Tuba; Ayvaz Deniz; Strauss Albee Dara M; Ersoy Evans Sibel; Tezcan Ilhan; Turkkani Gulten; Matthews Helen F; Haliloglu Goknur; Yuce Aysel; Yalcin Bilgehan; Gokoz Ozay; Oguz Kader K; Su Helen C

来源：Journal of Clinical Immunology, 2012, 32(4): 698-708.

DOI：10.1007/s10875-012-9664-5

• DOCK8
• combined immunodeficiency
• epidermodysplasia verruciformis
• sclerosing cholangitis
• CNS lymphoma
• leiomyosarcoma

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%26apos; 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.

• 出版日期2012-8