Novel pathological genetic variant associated with DOCK8 deficiency: case report with successful hematopoietic stem cell transplantation
Allergologia et Immunopathologia, cilt.54, sa.4, ss.144-150, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 54 Sayı: 4
- Basım Tarihi: 2026
- Doi Numarası: 10.15586/aei.v54i4.1585
- Dergi Adı: Allergologia et Immunopathologia
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, DIALNET, Health Research Premium Collection (ProQuest)
- Sayfa Sayıları: ss.144-150
- Anahtar Kelimeler: DOCK8 deficiency, hematopoietic cell transplantation, hyper-IgE, inborn errors of immunity
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Karadeniz Teknik Üniversitesi Adresli: Evet
Özet
Deficiency of dedicator of cytokinesis 8 (DOCK8) is a combined immunodeficiency characterized by severe atopic dermatitis, recurrent infections, and elevated serum immunoglobulin E (IgE) levels. Following genetic confirmation, early hematopoietic stem cell transplantation (HSCT) is the treatment of choice. We report a 7-year-old girl who presented with refractory atopic dermatitis and recurrent sinopulmonary infections. Laboratory evaluation revealed markedly elevated total IgE, lymphopenia, decreased memory B cells, and poor vaccine responses. Whole exome sequencing identified a previously unreported homozygous nonsense mutation in the DOCK8 gene (c.5382C>A; p.Tyr1794*). Functional validation was achieved through flow cytometry, which demonstrated significantly reduced DOCK8 protein expression. The patient underwent successful HSCT from a fully matched (10/10) HLA-compatible donor following conditioning with fludarabine and treosulfan. At 1 year follow-up, full donor chimerism was achieved, and the patient remained in remission. This case highlights a novel pathogenic variant in DOCK8 deficiency and demonstrates curative success following definitive diagnosis and timely HSCT.