Clinical, immunological and molecular profiles of DOCK8 deficiency in six patients from a tertiary care centre in North India

Clin Exp Dermatol. 2024 Feb 14;49(3):226-234. doi: 10.1093/ced/llad345.


Background: Dedicator of cytokinesis protein 8 (DOCK8) deficiency is an autosomal recessive form of combined immunodeficiency. This rare disorder is characterized by an increased predisposition to allergy, autoimmunity and malignancies.

Objectives: To analyse clinical, immunological and molecular profiles of patients with DOCK8 deficiency.

Methods: Clinic records of all patients attending the primary immunodeficiency clinic from 2018 to 2021 were reviewed. Six patients from five families were found to have DOCK8 deficiency.

Results: Median age at diagnosis was 7.5 years (range 2-13), with a male/female ratio of 5 : 1. Among the six patients, recurrent eczematous skin lesions were the predominant cutaneous manifestation, present in five patients (83%). Warts and molluscum contagiosum were evident in two patients (33%) and one patient (16%), respectively. Two patients had recalcitrant prurigo nodularis lesions and two had epidermodysplasia verruciformis-like lesions. Food allergies and asthma were reported by one patient each. Of the six patients, recurrent sinopulmonary infections were detected in five (83%). Epstein-Barr virus-driven non-Hodgkin lymphoma with liver metastases was the only case of malignancy, in a 4-year-old boy. IgE was elevated in all patients. Lymphopenia and eosinophilia were observed in three patients (50%) and five patients (83.3%), respectively. Genetic analysis showed DOCK8 pathogenic variants in all patients: homozygous deletion mutations in two patients, compound heterozygous deletion mutations in one, and homozygous nonsense mutations in two. A novel pathogenic homozygous missense variant in the DOCK8 gene was identified in one patient.

Conclusions: DOCK8 deficiency should be considered as a possibility in any patient with early onset eczema, cutaneous viral infections and increased predisposition to allergy, autoimmunity and malignancy.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cytokinesis
  • Eczema* / genetics
  • Epstein-Barr Virus Infections*
  • Female
  • Guanine Nucleotide Exchange Factors / genetics
  • Herpesvirus 4, Human
  • Homozygote
  • Humans
  • Hypersensitivity*
  • Job Syndrome* / genetics
  • Male
  • Neoplasms*
  • Sequence Deletion
  • Tertiary Care Centers


  • DOCK8 protein, human
  • Guanine Nucleotide Exchange Factors