Poster Display Malignancy and PID

NOVEL HOMOZYGOUS MUTATION IN DEDICATOR OF CYTOKINESIS 8 GENE IN TWO SIBLINGS AT THE TWO DISTINCT ENDS OF THE DISEASE WITH DEVELOPMENT OF MALIGNANCY

Lecture Time
11:50 - 11:51
Presenter
  • Daifulah ALZAHRANI, Saudi Arabia
Room
Poster Area
Date
20.09.2019, Friday
Session Time
10:00 - 17:00
Board Number
8
Presentation Topic
Malignancy and PID

Abstract

Background and Aims

Dedicator of Cytokinesis 8 (DOCK8) deficiency; an autosomal recessive form of Hyper-IgE syndrome (HIGE), is primary immunodeficiency. It has various clinical manifestations including allergic diseases, high susceptibility to viral and bacterial infections, and high risk for malignancy.

Methods

We describe two siblings; 5-years old girl who was transferred to us with persistent fever for 1-month not-responding to antibiotics and renal mass for investigations. Since two months of age, she had recurrent purulent otitis media and pneumonias requiring hospitalizations for IV antibiotics. She has severe generalized dermatitis, and multiple food and drug allergies. The 2-years older sister was asymptomatic and healthy.

Results

The index patient was febrile with generalized dermatitis and lymphadenopathy. Her white blood cell counts; 14,000, neutrophils; 10,290, thrombocytes; 562,000 and lymphocytes; 1,990 with CD3+/CD4+/CD8+; 666 (cells/µL). Hemoglobin; 8.6g/dl, immunoglobulin-G;15g/L, immunoglobulin-M; 0.42g/L and immunoglobulin-E; 43,177IU/ml (N:25–440 IU/mL). Molecular genetic analysis revealed novel homozygous mutation in DOCK8 gene; chr9(GRCh37):g.368136G>T. DOCK8 variant c.1797+1G>T. Viral screen; EBV-PCR<40IU/ml and high Cytomegalovirus-PCR; 3,709IU/ml. CT scans: showed multiple pulmonary nodules, generalized lymphadenopathy and large right kidney mass. Histopathology of lymph node, lung and kidney biopsies confirmed high grad diffuse large B-cell lymphoma (stage-IV). She was started on standard chemotherapy protocol, but died due to Escherichia Coli sepsis and multiorgan failure. Genetic screen for her sister showed the same homozygous mutation.

Conclusions

DOCK8 deficiency is known to cause combined immunodeficiency and risk for malignancy. However, our described novel mutation in DOCK8 gene could be associated with positive gene modifier that caused discrepancy in the clinical manifestations of the disease.

Hide