GATA2 deficiency associated with copy number variation: A reference for considering inborn errors of immunity
Clinical Implications Patients with chromosomal deletions or duplications, also known as copy number variants, may have associated inborn errors of immunity. A significant contribution to human genome variability can be attributed to CNVs, which are estimated to account for 4.8% to 9.7% of the human...
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| Published in: | The journal of allergy and clinical immunology in practice (Cambridge, MA) Vol. 10; no. 9; pp. 2476 - 2478.e9 |
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| Main Authors: | , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
Elsevier Inc
01-09-2022
Elsevier Limited |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Clinical Implications Patients with chromosomal deletions or duplications, also known as copy number variants, may have associated inborn errors of immunity. A significant contribution to human genome variability can be attributed to CNVs, which are estimated to account for 4.8% to 9.7% of the human genome.1 Copy number variants have three potential implications: no phenotypic effect, an adaptive trait, or underlying disease. Syndromes with numerical or structural chromosomal abnormalities are considered a distinct group within the classification of IEI.6 However, distinct chromosomal aberrations associated with immunodeficiency, other than those classified by the International Union of Immunological Societies (IUIS), have been reported in the literature.7 The patient in this report, as in many cases of immunodeficiency, did not present with classical features of GATA2 deficiency such as cutaneous viral skin infection, sensorineural hearing loss, or cytopenias. In the evaluation of possible immunodeficiency, it is imperative for any associated CNV to be analyzed carefully for the potential inclusion of a cytogenetic location incorporating a known causative gene of IEI.Online Repository Immune parameter May 2017 September 2017 December 2018 August 2020 WCC (K/μL) (reference range, 4-12 K/μL) 5.0 6.2 5.3 ALC (K/μL) (reference range, 0.6-7.8 K/μL) 0.9 2.0 1.2 ANC (K/μL) (reference range, 1-6 K/μL) 3.9 3.8 3.5 AMC (K/μL) (reference range, 0.1-1.8 K/μL) 0.3 0.2 0.5 CD3+ (cells/mm3) (reference range, (1,400-3,700 cells/mm3) 741 713 CD4+ (cells/mm3) (reference range, 700-2,200 cells/mm3) 351 340 CD8+ (cells/mm3) (reference range, 490-1,300 cells/mm3) 312 265 CD4/CD8 ratio (reference range, (0.9/2.6) 1.13 1.28 CD19+ (cells/mm3) (reference range, 270-860 cells/mm3) 247 184 CD16/56+ (cells/mm3) (reference range, 78-470 cells/μL) 384 220 CD45RA (reference range, 250-2,000 cells/μL) 123 184 CD45RO (reference range, (100-510 cells/μL) 167 152 CD27+ percentage of CD19+ B cells (reference range, (6.3% to 52.8%) 7 CD27+IgD– percentage of CD19+ B cells (reference range, 2.3% to 26.5%) 4 CD27+IgD+ percentage of CD19+ B cells (reference range, 1.7% to 29.3%) 4 CD21+CD27– percentage of CD19+ B cells (reference range, 92.1% to 99.6%) 91 CD21–CD27+ percentage of CD19+ B cells (reference range, 0.2% to 8.6%) 0 T-cell proliferation to mitogens (ConA, PHA, and CD3 ligation) Normal IgG (mg/dL) (reference range, 592-1,723 mg/dL) 381 425 672 IgA (mg/dL) (reference range, 33-235 mg/dL) 26 24 58 IgM (mg/dL) (reference range, 36-314 mg/dL) 34 26 36 Streptococcus pneumoniae serotypes 0/23 protective 15/23 protective 6/23 protective 4/23 protective Tetanus titer protective ≥ 0.01 IU/m 0.54 0.64 Diphtheria titer protective ≥ 0.01 IU/mL 0.2 0.16 Hemophilus titer protective ≥ 1.00 μg/mL 0.0 >9.0 8.8 Total hemolytic complement (reference range, 31-60 U/mL) >60 DHR Normal HIV Negative Table I Immune evaluation and dates Features GATA2 deficiency Index patient Hematologic Bone marrow failure, cytopenias involving B, natural killer, dendritic cell, CD4+, monocytes, macrophages B- and T-cell lymphopenia, micromegakaryoctyes on bone marrow biopsy Myeloid neoplasia AML, MDS, CMML, MPN Absent Auditory Sensorineural hearing loss Normal hearing Infectious Viral, bacterial, non-tuberculous mycobacterial and fungal infections Recurrent viral URI, Escherichia coli, Klebsiella UTI, suspected bacterial pneumonia with parapneumonic effusion Lymphatic Lymphedema Absent Pulmonary Pulmonary alveolar proteinosis Absent Table II Characteristic features of GATA2 deficiency versus patient features 1p22.1 GFI1 GFI1 deficiency (SCN2) AD 1p22.3 Bcl10 Bcl10 deficiency AR 1p31.3 IL12RB2 Il-12 receptor β2 deficiency AR 1p31.3 IL23R IL-23 receptor deficiency AR 1p31.3 JAK1 JAK1 deficiency AR LOF 1p32.1 C8A C8α deficiency (C8 deficiency, type 1) AR 1p32.1 MYSM1 MYSM1 deficiency AR 1p32.2 C8B C8β deficiency (C8 deficiency, type II) AR 1p34.2 CTPS1 CTPS1 deficiency AR 1p34.3 CSF3R G-CSF deficiency AR 1p35.1 AK2 AK2 deficiency (T-B-NK-SCID) AR 1p35.2 LCK LCK deficiency AR 1p36.11 FCN3 Ficolin 3 deficiency AR 1p36.12 C1QA C1q deficiency AR 1p36.12 C1QB C1q deficiency AR 1p36.12 C1QC C1q deficiency AR 1p36.12 CDC42 Multisystem inflammatory disease AD 1p36.22 PIK3CD p110δ deficiency; activated P110δ syndrome AR; AD GOF |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 2213-2198 2213-2201 |
| DOI: | 10.1016/j.jaip.2022.05.020 |