First patient in the Iranian Registry with novel DOCK2 gene mutation, presenting with skeletal tuberculosis, and review of literature

Allergy, Asthma & Clinical Immunology

Araz Sabzevari¹  Arash Kalantari²  Amirhosein Noohi³  Yasaman Aminpour³  Niusha Sharifinejad⁴  Homa Sadri⁵  Gholamreza Azizi⁶  Samaneh Delavari⁷ 

[1] CinnaGen Medical Biotechnology Research Center, Alborz University of Medical Sciences, Karaj, Iran;Department of Immunology and Allergy, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran;Department of Pediatrics, Imam Ali Hospital, Alborz University of Medical Sciences, Karaj, Iran;Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran;Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran;Department of Pediatrics, Imam Ali Hospital, Alborz University of Medical Sciences, Karaj, Iran;Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran;Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Science, Tehran, Iran;Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Science, Tehran, Iran;

关键词: Primary Immunodeficiency;    Dedicator of cytokinesis 2 deficiency;    DOCK2 deficiency;    Combined immunodeficiency;    CID;   

DOI  :  10.1186/s13223-021-00631-5

来源: Springer

【 摘 要 】

BackgroundDedicator of cytokinesis 2 (DOCK2) deficiency is an inborn error of immunity characterized by cellular and humoral immunological abnormalities leading to early-onset infections.Case presentationWe reported a novel case of a 27 months old girl presenting with recurrent pneumonia and a history of skeletal tuberculosis at the age of 19-month-old. Her immunological workup revealed persistent lymphopenia and low CD4 + T cell count along with elevated levels of CD19 +, CD20 +, CD16 +, and CD56 + cells. Furthermore, she had a high level of immunoglobulin (Ig) E and a slightly reduced IgM level with a non-protective antibody titer against diphtheria. The whole-exome sequencing (WES) analysis identified a homozygous frameshift deletion mutation (c.1512delG, p.I505Sfs*28) in exon 16 of the DOCK2 gene. We also conducted electronic searches in PubMed, Web of Science, and Scopus databases and reviewed the articles reporting patients with DOCK2 deficiency. The literature search yielded 14 DOCK2-deficient patients suffering from both cellular and humoral immune defects leading to early-onset infections, particularly human herpesvirus (HHV) infection.ConclusionDOCK2 deficiency should be considered in the context of severe or unusual early-onset infections, especially HHV infections, in a patient with a probable clinical diagnosis of combined immunodeficiency. We also recommended that DOCK2-deficient patients might benefit from T-cell receptor excision circle (TREC) assay as part of the routine newborn screening program.

【 授权许可】

CC BY