Salzer et al. (2013) reported a 12-year-old boy, born of consanguineous Turkish parents, with a primary immune deficiency syndrome characterized by B-cell deficiency and severe autoimmunity. He had recurrent infections involving most systems (respiratory, urinary, gastrointestinal) beginning in ... Salzer et al. (2013) reported a 12-year-old boy, born of consanguineous Turkish parents, with a primary immune deficiency syndrome characterized by B-cell deficiency and severe autoimmunity. He had recurrent infections involving most systems (respiratory, urinary, gastrointestinal) beginning in the first year of life. At age 15 months, he developed autoimmune nephrotic syndrome; renal biopsy showed membranous glomerulonephritis with IgG and complement component deposits. By age 3 years, he had hepatosplenomegaly and generalized lymphadenopathy associated with low-grade herpes viremia. Additional autoimmune features included polychondritis and antiphospholipid syndrome, with antinuclear, anti-dsDNA, and anticardiolipin IgG antibodies. He was treated with IV IgG at age 4 years, which resulted in a decrease in infections, and with anti-CD20 therapy, but autoantibodies persisted. Initial immunologic work-up showed low IgG with increased IgA and IgM. The formal criteria of CVID, which includes decreased levels of at least 2 classes of Ig were not met, but the phenotype was consistent with a CVID-like disorder. B-cell studies showed a reduction of CD19+ B cells, decreased memory B cells, and increased CD21(low) B cells. T-cell studies showed mildly decreased proliferative responses. The patient's father had Behcet disease and mild autoimmune thyroiditis at age 40 years, whereas his mother was asymptomatic.
In a patient with CVID9, Salzer et al. (2013) identified a homozygous splice site mutation in the PRKCD gene (176977.0001). The mutation was found by homozygosity mapping and exome sequencing and segregated with the disorder in the family. ... In a patient with CVID9, Salzer et al. (2013) identified a homozygous splice site mutation in the PRKCD gene (176977.0001). The mutation was found by homozygosity mapping and exome sequencing and segregated with the disorder in the family. Western blot analysis showed absent expression of the PRKCD protein in patient cells and decreased expression in cells from the heterozygous father. Patient cells showed defective phosphorylation of MARCKS (177061), a downstream target of PRKCD, as well as increased IL6 (147620) production after stimulation. Genetic analysis also revealed a heterozygous variant (dbSNP rs231775) in the CTLA4 gene (123890.0001) in the patient and his father, which may have acted as a disease modifier given its association with autoimmune disorders.